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66 results on '"Pathologie morphologique"'

1. Upfront surgery or definitive radiotherapy for p16+ oropharyngeal cancer. A GETTEC multicentric study

Author: Laure Santini, Agnès Dupret-Bories, Haitham Mirghani, Aicha Ben Lakdar, Pascal Roger, Guillaume Chambon, Olivier Dassonville, Françoise Chapel, Emmanuel Chamorey, Julien Viotti, Sébastien Vergez, Thibault Galissier, Karen Benezery, Valérie Coste, Benjamin Lallemant, Stéphane Temam, D. Culié, Alexandre Bozec, Nicolas Fakhry, Bruno Guelfucci, Frederic Peyrade, Anne Sophie Ramay, Anne Sudaka, Florence Jourdan-Soulier, P. Gorphe, Alain Bizeau, Gilles Poissonnet, Joanne Guerlain, Renaud Garrel, Esma Saada-Bouzid, A. Modesto, Renaud Schiappa, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Montpellier (UM), Université Côte d'Azur (UCA)-UNICANCER, CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Survival, medicine.medical_treatment, Oropharynx, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human papilloma virus, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Humans, Medicine, In patient, 030223 otorhinolaryngology, Definitive radiotherapy, Cyclin-Dependent Kinase Inhibitor p16, Cancer, Aged, Neoplasm Staging, Retrospective Studies, Chemotherapy, Radiotherapy, business.industry, Papillomavirus Infections, Univariate, Chemoradiotherapy, Adjuvant, Induction Chemotherapy, General Medicine, Middle Aged, medicine.disease, 3. Good health, Surgery, Survival Rate, Radiation therapy, Oropharyngeal Neoplasms, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, Female, Radiotherapy, Adjuvant, Cisplatin, Neoplasm Recurrence, Local, business
Abstract: International audience; Background: The aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC.Methods: All p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS).Results: 382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis.Conclusion: In p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS.
Published: 2021

2. An epitranscriptomic mechanism underlies selective mRNA translation remodelling in melanoma persister cells

Author: Jean-Yves Scoazec, Sara Faouzi, Amandine Bastide, Fabrice Andre, Shensi Shen, Séverine Roy, Emilie Routier, Hélène Malka-Mahieu, Caroline Robert, Yu Fu, Laurent Désaubry, Alexandre David, Alexander M.M. Eggermont, Stéphan Vagner, Xiaoxiao Sun, Christine Mateus, Sylvain Martineau, Université de Picardie Jules Verne (UPJV), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Stress génotoxiques et cancer, Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Nanjing University (NJU), Département Interdisciplinaire de Soins de Support aux Patients en Onco-hématologie [Gustave Roussy] (DISSPO), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pathologie mammaire, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Cardio-Oncologie et Chimie Médicinale, and Centre National de la Recherche Scientifique (CNRS)
Subjects: Untranslated region, Adenosine, Skin Neoplasms, Transcription, Genetic, [SDV]Life Sciences [q-bio], Aucun, General Physics and Astronomy, Epigenesis, Genetic, Eukaryotic initiation factor 4F, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Protein biosynthesis, genetics, lcsh:Science, Melanoma, ComputingMilieux_MISCELLANEOUS, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Chemistry, food and beverages, Translation (biology), MAP Kinase Kinase Kinases, RNA Helicase A, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, Cancer therapeutic resistance, 030220 oncology & carcinogenesis, RNA Helicases, Proto-Oncogene Proteins B-raf, Science, drug effects, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, drug therapy, pathology, antagonists & inhibitors, Cell Line, Tumor, Humans, analogs & derivatives, metabolism, RNA, Messenger, Protein Kinase Inhibitors, 030304 developmental biology, fungi, General Chemistry, DNA Methylation, pharmacology, therapeutic use, Cell culture, Drug Resistance, Neoplasm, eIF4A, Eukaryotic Initiation Factor-4A, Mutation, lcsh:Q, 5' Untranslated Regions
Abstract: Cancer persister cells tolerate anticancer drugs and serve as the founders of acquired resistance and cancer relapse. Here we show that a subpopulation of BRAFV600 mutant melanoma cells that tolerates exposure to BRAF and MEK inhibitors undergoes a reversible remodelling of mRNA translation that evolves in parallel with drug sensitivity. Although this process is associated with a global reduction in protein synthesis, a subset of mRNAs undergoes an increased efficiency in translation. Inhibiting the eIF4A RNA helicase, a component of the eIF4F translation initiation complex, abrogates this selectively increased translation and is lethal to persister cells. Translation remodelling in persister cells coincides with an increased N6-methyladenosine modification in the 5′-untranslated region of some highly translated mRNAs. Combination of eIF4A inhibitor with BRAF and MEK inhibitors effectively inhibits the emergence of persister cells and may represent a new therapeutic strategy to prevent acquired drug resistance., Melanoma persister cells are tolerant to anti-BRAF and anti-MEK inhibition and can trigger cancer relapse. Here the authors show that a subset of N6-methyladenosine modified mRNAs is translationally activated in persister cells. This preferential translation can be abrogated via eIF4A inhibition.
Published: 2019

3. Molecular genotyping in refractory thyroid cancers in 2021: When, how and why? A review from the TUTHYREF network

Author: Slimane Zerdoud, Camille Buffet, Stéphane Bardet, Abir Al Ghuzlan, Myriam Decaussin-Petrucci, Johanna Wassermann, Sophie Leboulleux, Isabelle Borget, Yann Godbert, Fabien Calcagno, Christelle De La Fouchardiere, Christine Do Cao, Françoise Borson Chazot, Centre Léon Bérard [Lyon], Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Hospices Civils de Lyon (HCL), CHU Lille, Institut E3M [CHU Pitié-Salpêtrière], Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Bergonié [Bordeaux], UNICANCER, Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], and HAL-SU, Gestionnaire
Subjects: Oncology, Cancer Research, medicine.medical_specialty, TUTHYREF, medicine.medical_treatment, Locally advanced, BRAF, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, 030304 developmental biology, International level, 0303 health sciences, Refractory thyroid cancer, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Thyroid, Cancers thyroïdiens réfractaires, Inhibiteurs de kinase, Treatment options, Hematology, General Medicine, Molecular genotyping, 3. Good health, Radiation therapy, medicine.anatomical_structure, ALK, Kinase inhibitors, 030220 oncology & carcinogenesis, business, RET, NTRK, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Refractory thyroid cancers include radio-iodine-refractory cancers, metastatic or locally advanced unresectable medullary and anaplastic thyroid cancers. Their management has been based for several years on the use of multi-target kinase inhibitors, with anti-angiogenic action, with the exception of anaplastic cancers usually treated with chemo- and radiotherapy. The situation has recently evolved due to the availability of molecular genotyping techniques allowing the discovery of rare but targetable molecular abnormalities. New treatment options have become available, more effective and less toxic than the previously available multi-target kinase inhibitors. The management of refractory thyroid cancers is therefore becoming more complex both at a diagnosis level with the need to know when, how and why to look for these molecular abnormalities but also at a therapeutic level, innovative treatments being hardly accessible. The cost of molecular analyzes and the access to treatments need also to be homogenized because disparities could lead to inequality of care at a national or international level. Finally, the strategy of identifying molecular alterations and treating these rare tumors reinforces the importance of a discussion in a multidisciplinary consultation meeting., Les cancers thyroïdiens réfractaires regroupent les cancers de souche folliculaire réfractaires à l’iode, les cancers médullaires métastatiques ou localement avancés non résécables et les cancers anaplasiques. Leur prise en charge est basée depuis quelques années sur l’utilisation d’inhibiteurs de kinase multicibles, à action principalement anti-angiogénique, exception faite des cancers anaplasiques habituellement traités par chimio- et radiothérapie. La situation a récemment évolué en raison de la mise à disposition de techniques de génotypage moléculaire permettant la découverte d’anomalies moléculaires rares mais ciblables, et de nouveaux traitements, possiblement plus efficaces et moins toxiques que les inhibiteurs de kinase multicibles préalablement disponibles. La prise en charge de ces cancers se complexifie donc à la fois au niveau diagnostique avec la nécessité de savoir quand, comment et pourquoi rechercher ces anomalies moléculaires mais également au niveau thérapeutique, avec la question de la disponibilité des traitements innovants et de l’accès aux essais cliniques. Le coût des analyses moléculaires et l’accès aux médicaments sont à harmoniser car des disparités pourraient conduire à une inégalité des soins au niveau national ou international. Enfin, la stratégie d’identification des altérations moléculaires et de traitement pour ces tumeurs rares renforce l’importance d’une discussion en réunion de concertation pluridisciplinaire.
Published: 2021

4. Génotypage moléculaire dans les cancers réfractaires de la thyroïde en 2021 : quand, comment, et pourquoi ? Un travail du réseau TUTHYREF

Author: De La Fouchardière, Christelle, Wassermann, Johanna, Calcagno, Fabien, Bardet, Stéphane, Al Ghuzlan, Abir, Borget, Isabelle, Borson Chazot, Françoise, Do Cao, Christine, Buffet, Camille, Zerdoud, Slimane, Decaussin-Petrucci, Myriam, Godbert, Yann, Leboulleux, Sophie, Centre Léon Bérard [Lyon], Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Hospices Civils de Lyon (HCL), CHU Lille, Institut E3M [CHU Pitié-Salpêtrière], Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER, Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Refractory thyroid cancer, ALK, Kinase inhibitors, TUTHYREF, Cancers thyroïdiens réfractaires, Inhibiteurs de kinase, RET, NTRK, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, BRAF
Abstract: International audience; Refractory thyroid cancers include radio-iodine-refractory cancers, metastatic or locally advanced unresectable medullary and anaplastic thyroid cancers. Their management has been based for several years on the use of multi-target kinase inhibitors, with anti-angiogenic action, with the exception of anaplastic cancers usually treated with chemo- and radiotherapy. The situation has recently evolved due to the availability of molecular genotyping techniques allowing the discovery of rare but targetable molecular abnormalities. New treatment options have become available, more effective and less toxic than the previously available multi-target kinase inhibitors. The management of refractory thyroid cancers is therefore becoming more complex both at a diagnosis level with the need to know when, how and why to look for these molecular abnormalities but also at a therapeutic level, innovative treatments being hardly accessible. The cost of molecular analyzes and the access to treatments need also to be homogenized because disparities could lead to inequality of care at a national or international level. Finally, the strategy of identifying molecular alterations and treating these rare tumors reinforces the importance of a discussion in a multidisciplinary consultation meeting.; Les cancers thyroïdiens réfractaires regroupent les cancers de souche folliculaire réfractaires à l’iode, les cancers médullaires métastatiques ou localement avancés non résécables et les cancers anaplasiques. Leur prise en charge est basée depuis quelques années sur l’utilisation d’inhibiteurs de kinase multicibles, à action principalement anti-angiogénique, exception faite des cancers anaplasiques habituellement traités par chimio- et radiothérapie. La situation a récemment évolué en raison de la mise à disposition de techniques de génotypage moléculaire permettant la découverte d’anomalies moléculaires rares mais ciblables, et de nouveaux traitements, possiblement plus efficaces et moins toxiques que les inhibiteurs de kinase multicibles préalablement disponibles. La prise en charge de ces cancers se complexifie donc à la fois au niveau diagnostique avec la nécessité de savoir quand, comment et pourquoi rechercher ces anomalies moléculaires mais également au niveau thérapeutique, avec la question de la disponibilité des traitements innovants et de l’accès aux essais cliniques. Le coût des analyses moléculaires et l’accès aux médicaments sont à harmoniser car des disparités pourraient conduire à une inégalité des soins au niveau national ou international. Enfin, la stratégie d’identification des altérations moléculaires et de traitement pour ces tumeurs rares renforce l’importance d’une discussion en réunion de concertation pluridisciplinaire.
Published: 2021

5. Well-Differentiated Papillary Mesothelioma of the Peritoneum: A Retrospective Study from the RENAPE Observational Registry

Author: Guillaume, Vogin, Liza, Hettal, Jean-Michel, Vignaud, Peggy, Dartigues, Diane, Goere, Gwenaël, Ferron, Bruno, Heyd, Jean-Marc, Bereder, Jean-Jacques, Tuech, Olivier, Glehen, Cécile, de Chaisemartin, Yoann, Lherm, Laurent, Villeneuve, Vahan, Kepenekian, Frédéric, Marchal, Franck, Zinzindohoue, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Département de chirurgie viscérale [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Claudius Regaud, Service d'oncologie chirurgicale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Département de chirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche en Automatique de Nancy (CRAN), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: Adult, Male, Mesothelioma, medicine.medical_specialty, Malignancy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Carcinoma, Humans, Registries, Survival rate, Peritoneal Neoplasms, Aged, Retrospective Studies, business.industry, Cancer, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Retrospective cohort study, Cytoreduction Surgical Procedures, Hyperthermia, Induced, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carcinoma, Papillary, 3. Good health, Surgery, Survival Rate, Oncology, Chemotherapy, Cancer, Regional Perfusion, 030220 oncology & carcinogenesis, Peritoneal Cancer Index, Female, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, business, Follow-Up Studies
Abstract: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare entity. Questions regarding management are still being debated as no more than 50 cases have been reported in the literature. We aimed to analyze the clinical, therapeutic, and prognostic data of patients with WDPMP from the RENAPE observational registry. All patients diagnosed with WDPMP and prospectively included in the RENAPE national registry between 2010 and 2018 were also included in our study. Expert pathologists from the RENA-PATH group confirmed all cases. All clinical, therapeutic, postoperative, and prognostic data were extracted and analyzed. We report on 56 patients with a mean age of 52 years (range 21–74). WDPMP was incidentally diagnosed during imaging or surgery in 16% and 36% of patients, respectively, and an association with synchronous malignancy was found in 18% of patients. Nine lesions showed discrete signs of fatty invasion. The median Peritoneal Cancer Index was 11 (range 0–33). Eleven patients were treated with definitive excision, 4 were treated with cytoreductive surgery (CRS) only, 37 were treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), and 2 were treated with CRS plus HIPEC plus early postoperative intraperitoneal chemotherapy. CRS was considered to be complete in 90% of cases. One patient died postoperatively and 16 patients (31%) faced postoperative complications. The median disease-free survival was 144 months; Four patients relapsed, with a median period of 27 months. No prognostic factors could be identified. Our analysis confirms the favorable prognosis of WDPMP. CRS and HIPEC could be a therapeutic option for diffuse, symptomatic, and/or recurrent disease.
Published: 2019

6. Peritoneal or mesenteric tumours revealing histiocytosis

Author: Janick Selves, Sébastien Humbert, Peggy Dartigues, Manuela Delage-Corre, Chrystalla Prokopiou, Liana Veresezan, Jean Donadieu, Séverine Valmary-Degano, Patrick Tas, Olivier Lucidarme, Frédéric Charlotte, Andreas Seeber, Alexandre Malakhia, Julien Haroche, Zofia Hélias-Rodzewicz, Jerome Razanamahery, Fleur Cohen-Aubart, Merja Kunnamo, Abdellatif Tazi, Irena Ungureanu, Dominique Cazals-Hatem, Jean-François Emile, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Ambroise Paré [AP-HP], Emergency Hospital Floreasca Bucharest, Emergency Hospital Floreasca Bucharest, 8 Calea Floresca, Sector 1, 014461 Bucharest, Romania, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Limoges, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Limassol General Hospital, Innsbruck Medical University [Austria] (IMU), Hopital Saint-Louis [AP-HP] (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Pitié-Salpétrière], Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Proto-Oncogene Proteins B-raf, Abdominal pain, Pathology, medicine.medical_specialty, Delayed Diagnosis, [SDV]Life Sciences [q-bio], RC799-869, Liposarcoma, Sclerosing mesenteritis, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Medicine, molecular biology, Humans, Mesentery, Histiocyte, Cancer, Retrospective Studies, business.industry, CD68, Gastroenterology, abdominal pain, Diseases of the digestive system. Gastroenterology, medicine.disease, 3. Good health, Histiocytosis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Histiocytoses, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: ObjectivePeritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process.DesignWe performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes.ResultsAbdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease.ConclusionDiagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.
Published: 2021

7. False negative rate at 18F-FDG PET/CT in para-aortic lymphnode involvement in patients with locally advanced cervical cancer: impact of PET technology

Author: Amandine Maulard, Catherine Genestie, Marie Terroir, Sebastien Gouy, Alexandra Leary, Patricia Pautier, Serena Grimaldi, Cyrus Chargari, Veronika Seebacher, Désirée Deandreis, Philippe Morice, Anna Ilenko, Malbec, Odile, Département de chirurgie gynécologique [Gustave Roussy], Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département de radiothérapie [Gustave Roussy], Institut de Recherche Biomédicale des Armées (IRBA), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Università degli studi di Torino = University of Turin (UNITO), Imagerie thérapeutique (radiologie interventionnelle), and University of Turin
Subjects: Cancer Research, [SDV]Life Sciences [q-bio], Cervical cancer, FDG, LACC, Para-aortic lymph node, PET/CT, TOF, Adenocarcinoma, Adult, Aged, Aorta, Carcinoma, Squamous Cell, Chemoradiotherapy, False Negative Reactions, Female, Humans, Laparoscopy, Lymph Node Excision, Lymph Nodes, Middle Aged, Neoplasm Staging, Pelvis, Positron Emission Tomography Computed Tomography, Retrospective Studies, Uterine Cervical Neoplasms, Young Adult, Fluorodeoxyglucose F18, Radiopharmaceuticals, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Medicine, Stage (cooking), medicine.diagnostic_test, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, medicine.drug, lcsh:RC254-282, 03 medical and health sciences, Genetics, Fluorodeoxyglucose, PET-CT, business.industry, Carcinoma, Magnetic resonance imaging, medicine.disease, Squamous Cell, Lymphadenectomy, business, Nuclear medicine
Abstract: Background The identification of factors responsible for false negative (FN) rate at 18F- Fluorodeoxyglucose (FDG) Positron Emission Tomography /Computed Tomography (PET/CT) in para-aortic (PA) lymph nodes in the presurgical staging of patients with locally advanced cervical cancer (LACC) is challenging. The aim of this study was to evaluate the impact of PET/CT technology. Methods A total of 240 consecutive patients with LACC (International Federation of Gynecology and Obstetrics, FIGO, stage IB2-IVA) and negative Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and negative 18F-FDG PET/CT in the PA region, undergoing laparoscopic PA lymphadenectomy before chemoradiotherapy were included. The FN rate in patients studied with Time of flight (TOF) PET/CT (TOF PET) or non-Time of flight PET/CT (no-TOF PET) technology was retrospectively compared. Results Patients presented with FIGO stage IB (n = 78), stage IIA-B (n = 134), stage III (n = 18) and stage IVa (n = 10), squamous cell carcinoma (n = 191) and adenocarcinoma (n = 49). 141/240 patients were evaluated with no-TOF PET/CT and 99/240 with TOF PET/CT. Twenty-two patients (9%) had PA nodal involvement at histological analysis and considered PET/CT FN findings. The FN rate was 8.5% for no-TOF PET and 10% for TOF PET subgroup respectively (p = 0.98). Ninety patients (38%) presented with pelvic node uptakes at PET/CT. The FN rate in the PA region was 18% (16/90) and 4% (6/150) in patients with and without pelvic node involvement at PET/CT respectively (19 vs 3% for no-TOF PET and 17 vs 5% for TOF PET subgroup). Conclusions In LACC, FN rate in PA lymph nodes detection is a clinical issue even for modern PET/CT, especially in patients with pelvic uptake. Surgical lymphadenectomy should be performed in case of negative PET/CT at PA level in these patients, while it could be discussed in the absence of pelvic uptake.
Published: 2021

8. La carence en PBRM1 dans le cancer est létale de synthèse avec les inhibiteurs de réparation de l'ADN

Author: Chabanon, Roman M, Morel, Daphné, Eychenne, Thomas, Colmet-Daage, Léo, Bajrami, Ilirjana, Dorvault, Nicolas, Garrido, Marlène, Meisenberg, Cornelia, Lamb, Andrew, Ngo, Carine, Hopkins, Suzanna R, Roumeliotis, Theodoros I, Jouny, Samuel, Hénon, Clémence, Kawai-Kawachi, Asuka, Astier, Clémence, Konde, Asha, Nery, Elaine Del, Massard, Christophe, Pettitt, Stephen J, Margueron, Raphaël, Choudhary, Jyoti S, Almouzni, Geneviève, Soria, Jean-Charles, Deutsch, Eric, Downs, Jessica A, Lord, Christopher J, Postel-Vinay, Sophie, Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Dynamique du noyau, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Direction de la recherche [Gustave Roussy], The institute of cancer research [London], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ATIP-Avenir INSERM
Subjects: ATR inhibitors, [SDV]Life Sciences [q-bio], R-loop, PBRM1 deficiency, cGAS/STING, PARP inhibitors, synthetic lethality
Abstract: Polybromo 1 (PBRM1), a subunit of the PBAF chromatin-remodeling complex, is recurrently inactivated in cancer. To uncover novel synthetic lethal (SL) approaches for targeting PBRM1-defective cancers, we used a series of orthogonal functionalgenomic screens which identified SL between PBRM1 deficiency and inhibition of PARP1. This effect was elicited with clinical PARP inhibitors in vitro and in vivo and also operated when PARP inhibitors were combined with ATR inhibitors. These SL effects were characterized by pre-existing replication stress in PBRM1-defective cells and an increase in R-loops, micronuclei and tumor cell-autonomous cGAS/STING signaling in response to PARP inhibitors. Quantitative mass spectrometry indicated that PBRM1-defective cells exhibited downregulation of multiple R-loop processing factors, and exogenous expression of the R-loop resolution enzyme RNase H1 partially reversed PARP inhibitor sensitivity, providing a mechanistic rationale for the SL effects. Our data provide the preclinical basis for using PARP inhibitors in PBRM1-defective cancers.; Le polybromo 1 (PBRM1), une sous-unité du complexe PBAF remodelant la chromatine, est inactivé de manière récurrente dans le cancer. Pour découvrir de nouvelles approches létales synthétiques (SL) pour cibler les cancers défectueux PBRM1, nous avons utilisé une série de tests fonctionnels orthogonaux qui a permis d'identifier la SL entre la déficience en PBRM1 et l'inhibition de la PARP1.Cet effet a été obtenu avec des inhibiteurs cliniques de PARP in vitro et in vivo et a également fonctionné lorsque les inhibiteurs PARP ont été combinés avec les inhibiteurs ATR. Ces effets SL étaient caractérisés par un stress de réplication préexistant dans les cellules déficientes en PBRM1 et une augmentation des boucles R, des micronoyaux et des cellules tumorales - cGAS/STING autonomes en réponse aux inhibiteurs PARP. La spectrométrie de masse quantitative a indiqué que les cellules défectueuses PBRM1 présentaient une régulation à la baisse du traitement en boucle R multiple et l'expression exogène de l'enzyme de résolution de la boucle R, la RNase H1 a partiellement inversé la sensibilité aux inhibiteurs PARP, ce qui fournit une justification mécaniste des effets SL. Nos données fournissent la base préclinique de l'utilisation des inhibiteurs PARP dans les PBRM1- les cancers défectueux.
Published: 2020

9. PBRM1 deficiency in cancer is synthetic lethal with DNA repair inhibitors

Author: Chabanon, Roman M, Morel, Daphné, Eychenne, Thomas, Colmet-Daage, Léo, Bajrami, Ilirjana, Dorvault, Nicolas, Garrido, Marlène, Meisenberg, Cornelia, Lamb, Andrew, Ngo, Carine, Hopkins, Suzanna R, Roumeliotis, Theodoros I, Jouny, Samuel, Hénon, Clémence, Kawai-Kawachi, Asuka, Astier, Clémence, Konde, Asha, Nery, Elaine Del, Massard, Christophe, Pettitt, Stephen J, Margueron, Raphaël, Choudhary, Jyoti S, Almouzni, Geneviève, Soria, Jean-Charles, Deutsch, Eric, Downs, Jessica A, Lord, Christopher J, Postel-Vinay, Sophie, Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Dynamique du noyau, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Direction de la recherche [Gustave Roussy], The institute of cancer research [London], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ATIP-Avenir INSERM
Subjects: ATR inhibitors, [SDV]Life Sciences [q-bio], R-loop, PBRM1 deficiency, cGAS/STING, PARP inhibitors, synthetic lethality
Abstract: Polybromo 1 (PBRM1), a subunit of the PBAF chromatin-remodeling complex, is recurrently inactivated in cancer. To uncover novel synthetic lethal (SL) approaches for targeting PBRM1-defective cancers, we used a series of orthogonal functionalgenomic screens which identified SL between PBRM1 deficiency and inhibition of PARP1. This effect was elicited with clinical PARP inhibitors in vitro and in vivo and also operated when PARP inhibitors were combined with ATR inhibitors. These SL effects were characterized by pre-existing replication stress in PBRM1-defective cells and an increase in R-loops, micronuclei and tumor cell-autonomous cGAS/STING signaling in response to PARP inhibitors. Quantitative mass spectrometry indicated that PBRM1-defective cells exhibited downregulation of multiple R-loop processing factors, and exogenous expression of the R-loop resolution enzyme RNase H1 partially reversed PARP inhibitor sensitivity, providing a mechanistic rationale for the SL effects. Our data provide the preclinical basis for using PARP inhibitors in PBRM1-defective cancers.; Le polybromo 1 (PBRM1), une sous-unité du complexe PBAF remodelant la chromatine, est inactivé de manière récurrente dans le cancer. Pour découvrir de nouvelles approches létales synthétiques (SL) pour cibler les cancers défectueux PBRM1, nous avons utilisé une série de tests fonctionnels orthogonaux qui a permis d'identifier la SL entre la déficience en PBRM1 et l'inhibition de la PARP1.Cet effet a été obtenu avec des inhibiteurs cliniques de PARP in vitro et in vivo et a également fonctionné lorsque les inhibiteurs PARP ont été combinés avec les inhibiteurs ATR. Ces effets SL étaient caractérisés par un stress de réplication préexistant dans les cellules déficientes en PBRM1 et une augmentation des boucles R, des micronoyaux et des cellules tumorales - cGAS/STING autonomes en réponse aux inhibiteurs PARP. La spectrométrie de masse quantitative a indiqué que les cellules défectueuses PBRM1 présentaient une régulation à la baisse du traitement en boucle R multiple et l'expression exogène de l'enzyme de résolution de la boucle R, la RNase H1 a partiellement inversé la sensibilité aux inhibiteurs PARP, ce qui fournit une justification mécaniste des effets SL. Nos données fournissent la base préclinique de l'utilisation des inhibiteurs PARP dans les PBRM1- les cancers défectueux.
Published: 2020

10. Long term follow-up of a large series of stage-II/III atypical proliferative serous ovarian tumors

Author: Amandine Maulard, Catherine Genestie, Matthieu Faron, Sophie Maria, Alexandra Leary, Sebastien Gouy, Philippe Morice, Patricia Pautier, Cyrus Chargari, Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département de chirurgie viscérale [Gustave Roussy], Département de chirurgie gynécologique [Gustave Roussy], Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Adult, Prognostic factor, medicine.medical_specialty, Adolescent, Long term follow up, [SDV]Life Sciences [q-bio], Ovary, Stage ii, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Overall survival, Medicine, Humans, Atypical proliferative serous tumor, Neoplasm Invasiveness, Aged, Cell Proliferation, Neoplasm Staging, Retrospective Studies, Ovarian Neoplasms, business.industry, Obstetrics and Gynecology, Large series, Middle Aged, Invasive implants, Prognosis, Survival Analysis, 3. Good health, Cystadenocarcinoma, Serous, Conservative treatment, [SDV] Life Sciences [q-bio], Serous fluid, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Extraovarian low-grade serous carcinoma, Female, Neoplasm Recurrence, Local, business, Follow-Up Studies, Noninvasive implants
Abstract: International audience; Background: The aim of this study was to assess prognostic factors and implications on further management in a large series of stage-II or III Atypical Proliferative Serous Tumors (APST) with a long-term follow-up.Patients and methods: Patients with APSTs and peritoneal implants treated in, or referred to, our institution were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free (DFS) and overall survival (OS) were analyzed.Results: Between 1971 and 2017, 212 patients were identified and followed (33 having invasive implants). After a median follow-up of 115 months, 70 recurrences were observed, 28 of them under the form of invasive disease. DFS at 5 years and 10 years was 73% and 62% respectively. The use of a conservative treatment (HR = 5.5[3.33-9.08], p < .0001), the presence of ≥3 peritoneal sites with implants (HR = 1.65[1.01-2.72], p = .045) were unfavorable prognostic factors for DFS. The presence of ≥3 peritoneal sites with implants (HR = 3.02[0.96-9.53], p = .049) and the presence of stromal microinvasion (HR = 3.19[1.12-9.1], p = .022) were unfavorable prognostic factors for OS. Non-conservative surgery (HR = 7[2.35-20.87], p = .0002), invasive implants (HR = 5.37[1.29-22.26], p = .013), and ≥ 3 peritoneal sites with implants (HR = 3.56 [1.11-11.39], p = .024) were identified as predictors of recurrence in the form of an invasive disease. Invasive implants were not associated with DFS (HR = 1.39[0.77-2.51], p = .27), nor OS (HR = 1.76[0.57-5.47], p = .32).Conclusion: After a long-term follow-up, type of peritoneal implants is no longer a prognostic factor for OS. Implants ≥3 peritoneal sites seem to impact significantly OS and then require a specific follow-up in this subgroup of patients.
Published: 2020

11. Association of metastatic pattern and molecular status in stage IV non-small cell lung cancer adenocarcinoma

Author: Anas Gazzah, David Planchard, Lambros Tselikas, Nathalie Lassau, Etienne Rouleau, Melodie Tazdait, Alison Dormieux, Caroline Caramella, Cécile Le Péchoux, Jordi Remon, Laura Mezquita, Paul Henry Cournede, Francesco Facchinetti, Frank Aboubakar, Ludovic Lacroix, Charles Naltet, Corinne Balleyguier, Julien Adam, Maria-Virginia Bluthgen, Pernelle Lavaud, Benjamin Besse, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR), Mathématiques et Informatique pour la Complexité et les Systèmes (MICS), CentraleSupélec-Université Paris-Saclay, Centro Integral Oncologico Clara Campal, Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Pathologie morphologique, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncologie thoracique, Département de médecine oncologique [Gustave Roussy], Département de radiothérapie [Gustave Roussy], Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11), UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (SLuc) Service de pneumologie
Subjects: Adult, Male, medicine.medical_specialty, Lung Neoplasms, Neoplasm metastasis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Bone Neoplasms, Gastroenterology, 030218 nuclear medicine & medical imaging, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Multimodal imaging, Carcinoma, Non-Small-Cell Lung, Internal medicine, Biomarkers, Tumor, medicine, Humans, Radiology, Nuclear Medicine and imaging, [MATH]Mathematics [math], Tropism, ComputingMilieux_MISCELLANEOUS, Aged, Neoplasm Staging, Retrospective Studies, Lung, Oncogene, business.industry, DNA, Neoplasm, General Medicine, Middle Aged, medicine.disease, 3. Good health, ErbB Receptors, Serous fluid, medicine.anatomical_structure, Lymphangitis, 030220 oncology & carcinogenesis, Mutation, Adenocarcinoma of lung, Adenocarcinoma, Female, Radiology, business, Brain metastasis
Abstract: OBJECTIVES: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. METHODS: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. RESULTS: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. CONCLUSION: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. KEY POINTS: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma.
Published: 2020

12. Lésions épithéliales de l’ovaire. Cas no 3

Author: Hélène Plouhinec, Catherine Genestie, Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], and Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR)
Subjects: Pathology, medicine.medical_specialty, Text mining, medicine.anatomical_structure, business.industry, [SDV]Life Sciences [q-bio], Medicine, Ovary, business, ComputingMilieux_MISCELLANEOUS, Pathology and Forensic Medicine
Abstract: International audience
Published: 2020

13. Lésions épithéliales de l’ovaire. Cas no 4

Author: Catherine Genestie, Hélène Plouhinec, Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], and Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR)
Subjects: Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, [SDV]Life Sciences [q-bio], Medicine, Ovary, business, ComputingMilieux_MISCELLANEOUS, Pathology and Forensic Medicine
Abstract: International audience
Published: 2020

14. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author: Laura Comerma, Marie-Christine Mathieu, Joel H. Saltz, Giancarlo Pruneri, Peter Savas, Shom Goel, Stephan Wienert, Paula I. Gonzalez-Ericsson, Lee Cooper, Sunil R. Lakhani, Stefan Michiels, Pawan Kirtani, Sarah N Dudgeon, Francesco Ciompi, Uday Kurkure, Manu M. Sebastian, Giuseppe Viale, Brandon D. Gallas, Mohamed Amgad, John M. S. Bartlett, Jan Hudecek, Torsten O. Nielsen, Elisabeth Specht Stovgaard, Huang-Chun Lien, Alexander J. Lazar, Johan Hartman, Yinyin Yuan, Rim S. Kim, Jeppe Thagaard, Ashish Sharma, Sylvia Adams, Matthew G. Hanna, Stephen M. Hewitt, Weijie Chen, David L. Rimm, Khalid AbdulJabbar, Sibylle Loibl, Jochen K. Lennerz, I-Chun Chen, Zsuzsanna Bago-Horvath, Mehrnoush Khojasteh, Frédérique Penault-Llorca, Katherine L. Pogue-Geile, Federico Rojo, Marcelo Luiz Balancin, David Moore, Stuart J. Schnitt, Roberto Salgado, Loes F. S. Kooreman, Sherene Loi, Jeremy P Braybrooke, Eva Balslev, Leonie Voorwerk, Sunil S. Badve, Elvire Roblin, Jennifer K. Kerner, Marleen Kok, Andrew H. Beck, Michael Barnes, Jeroen van der Laak, Carsten Denkert, W. Fraser Symmans, Zuzana Kos, Rajendra Singh, Anant Madabhushi, Christos Sotiriou, Sandra Demaria, Hugo M. Horlings, Department of Pathology, Herlev and Gentofte Hospital, The University of Sydney, Charité, Institute of Pathology, Translational Tumorpathology Unit, Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), European Institute of Oncology [Milan] (ESMO), University of Southern Queensland (USQ), Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Division of Pathology and Laboratory Medicine, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), University of the Sunshine Coast (USC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), German Breast Group (GBG), Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, The Netherlands Cancer Institute, The University of Texas M.D. Anderson Cancer Center [Houston], Medizinische Universität Wien = Medical University of Vienna, Computational Biomedicine Lab (CBL), University of Houston, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), German Breast Group, Medical University of Vienna, Department of Pathology, Amgad, Mohamed [0000-0001-7599-6162], Sharma, Ashish [0000-0002-1011-6504], Savas, Peter [0000-0001-5999-428X], Hudeček, Jan [0000-0003-1071-5686], Braybrooke, Jeremy P [0000-0003-1943-7360], Demaria, Sandra [0000-0003-4426-0499], Comerma, Laura [0000-0002-0249-4636], Badve, Sunil S [0000-0001-8861-9980], Symmans, W Fraser [0000-0002-1526-184X], Gonzalez-Ericsson, Paula [0000-0002-6292-6963], Rimm, David L [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hanna, Matthew G [0000-0002-7536-1746], Lazar, Alexander J [0000-0002-6395-4499], Bago-Horvath, Zsuzsanna [0000-0002-8555-7806], van der Laak, Jeroen AWM [0000-0001-7982-0754], Gallas, Brandon D [0000-0001-7332-1620], Kurkure, Uday [0000-0002-8273-7334], Cooper, Lee AD [0000-0002-3504-4965], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Computer science, [SDV]Life Sciences [q-bio], Review Article, DIGITAL PATHOLOGY, Tumour biomarkers, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Prognostic markers, 0302 clinical medicine, Breast cancer, Ecology,Evolution & Ethology, Visual scoring, Medicine and Health Sciences, Pharmacology (medical), Chemical Biology & High Throughput, Human Biology & Physiology, IN-SITU, Medicinsk bildbehandling, Genome Integrity & Repair, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, SOLID TUMORS, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Oncology, 030220 oncology & carcinogenesis, Tumour immunology, TILS, Tumor immunology, Genetics & Genomics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer imaging, lcsh:RC254-282, CLASSIFICATION, 03 medical and health sciences, Signalling & Oncogenes, STANDARDIZED METHOD, QUALITY-CONTROL, SDG 3 - Good Health and Well-being, BREAST-CANCER, Radiology, Nuclear Medicine and imaging, IMAGE-ANALYSIS, Computational & Systems Biology, Tumor-infiltrating lymphocytes, Digital pathology, Médecine pathologie humaine, Tumour Biology, Data science, Biomarker (cell), Cancérologie, Medical Image Processing, 030104 developmental biology, Workflow, T-CELLS
Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring., info:eu-repo/semantics/published
Published: 2020

15. Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41–BEVANEC randomized phase II study

Author: Thomas Walter, Guillaume Cadiot, Alice Gangloff, Catherine Lombard-Bohas, Aurélie Ferru, Céline Lepère, Astrid Lièvre, Nadia Bouarioua, Vincent Hautefeuille, Jean-Yves Scoazec, Farid Elhajbi, Romain Coriat, Victoire Granger, C. Lepage, Olivier Dubreuil, Jean-Emmanuel Kurtz, Eric Assenat, Denis Smith, Laetitia Dahan, David Malka, Olivia Hentic, Guillaume Roquin, Karine Le Malicot, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pontchaillou [Rennes], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Michallon, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université de Lille-UNICANCER, and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, Leucovorin, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Drug Administration Schedule, Gastroenteropancreatic, FOLFIRI, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Intestinal Neoplasms, medicine, Humans, Etoposide, Hepatology, business.industry, Gastroenterology, medicine.disease, Survival Analysis, Carboplatin, Carcinoma, Neuroendocrine, 3. Good health, Pancreatic Neoplasms, Clinical trial, Neuroendocrine Tumors, Regimen, Treatment Outcome, 030104 developmental biology, chemistry, Research Design, 030220 oncology & carcinogenesis, Neuroendocrine carcinoma, Camptothecin, Female, Fluorouracil, France, business, Progressive disease, medicine.drug
Abstract: IF 3.061; International audience; Introduction : Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment.Aim :PRODIGE 41–BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC.Materials and methods : The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy.Results : A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response.Conclusion :The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.
Published: 2018

16. Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study

Author: J. Guigay, Catherine Cardot-Bauters, Patricia Niccoli, H. Du Boullay, B. Delemer, M. Le Bras, Catherine Lombard-Bohas, Olivier Chabre, Pierre B. A. Lecomte, Jean-Yves Scoazec, Christine Binquet, Ph. Caron, P. Chanson, Marc Klein, Carmen Vulpoi, Pierre Goudet, F. Borson-Chazot, T. Aparicio, Vincent Rohmer, E. Cosson, Albert Beckers, I. Guilhem, Eric Baudin, Bruno Vergès, A. Tabarin, Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'endocrinologie, diabétologie et nutrition, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Cité (USPC)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Institut des Sciences de la Terre (ISTerre), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pontchaillou [Rennes], Service d'Endocrinologie (ANGERS - Endocrino), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Eq 4, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est-Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupement Hospitalier Lyon-Est (GHE), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Groupement Hospitalier Lyon-Est ( GHE ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de médecine nucléaire, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Université de Reims Champagne-Ardenne ( URCA ) -Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle ( CRESS - U1153 ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Sorbonne Paris Cité ( USPC ) -Hôpital Jean Verdier-Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Institut des Sciences de la Terre ( ISTerre ), Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers ( INSU - CNRS ) -Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ) -Université Joseph Fourier - Grenoble 1 ( UJF ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Endocrinologie ( ANGERS - Endocrino ), and CHU Angers
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Neuroendocrine tumors, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Gastroenterology, Metastasis, Cohort Studies, br-NETs, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, Internal medicine, Biopsy, Multiple Endocrine Neoplasia Type 1, Humans, Medicine, Survival analysis, Aged, Cause of death, medicine.diagnostic_test, business.industry, Large cell, Bronchial Neoplasms, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Neuroendocrine Tumors, 030104 developmental biology, survival in MEN1 patients, 030220 oncology & carcinogenesis, Cohort, Female, Surgery, business, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Follow-Up Studies, Cohort study
Abstract: IF 2.673; International audience; ObjectiveTo evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death.Summary background databr-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis.MethodsThe 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5–59.6] years by the Groupe d’étude des Tumeurs Endocrines was analyzed using time-to-event techniques.Resultsbr-NETs were found in 51 patients (4.8%, [95% CI 3.6–6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28–66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02–5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10−4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths.ConclusionsAround 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.
Published: 2017

17. NADPH Oxidase NOX4 Is a Critical Mediator of BRAFV600E-Induced Downregulation of the Sodium/Iodide Symporter in Papillary Thyroid Carcinomas

Author: Abderrahmane Al Bouzidi, Corinne Dupuy, Jérémy Cailloux, Juliana Cazarin, Jennifer R. Cracchiolo, James A. Fagin, Rabii Ameziane-El-Hassani, Aurore Carré, Martin Schlumberger, Jeffrey A. Knauf, Abir Al Ghuzlan, Mohammed El Mzibri, Naima Azouzi, Dana M. Hartl, Michel Polak, Abdelkarim Filali-Maltouf, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), LPP - Laboratoire de Phonétique et Phonologie - UMR 7018 (LPP), Université Sorbonne Nouvelle - Paris 3-Centre National de la Recherche Scientifique (CNRS), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biology and Mediacl Research Unit, Centre National de l'Energie, des Sciences et Techniques Nucléaires, Faculté des sciences, Laboratoire de microbiologie et biologie moléculaire, Université Mohammed V de Rabat [Agdal], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Sodium-iodide symporter, medicine.medical_specialty, endocrine system diseases, Physiology, Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, Papillary thyroid cancer, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, medicine, Molecular Biology, ComputingMilieux_MISCELLANEOUS, General Environmental Science, NADPH oxidase, biology, Chemistry, Thyroid, NOX4, Cell Biology, medicine.disease, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Symporter, biology.protein, Cancer research, General Earth and Planetary Sciences
Abstract: Aims: The BRAFV600E oncogene, reported in 40%–60% of papillary thyroid cancer (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS), and therefore with radioiodine refractoriness. Inhibition of mitogen-activated protein kinase (MAPK) pathway, constitutively activated by BRAFV600E, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAFV600E adaptive resistance. Recent studies pointed to a key role of transforming growth factor β (TGF-β) in BRAFV600E-induced effects. The reactive oxygen species (ROS)-generating NADPH oxidase NOX4, which is increased in PTC, has been identified as a new key effector of TGF-β in cancer, suggestive of a potential role in BRAFV600E-induced thyroid tumors. Results: Here, using two human BRAFV600E-mutated thyroid cell lines and a rat thyroid cell line expressing BRAFV600E in a conditional manner, we show tha...
Published: 2017

18. The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei

Author: Roger Feakins, Manuel Rodriguez-Justo, Peggy Dartigues, Norman J. Carr, Sylvie Isaac, Leslie H. Sobin, Marie Louise F. van Velthuysen, Reetesh K. Pai, Frédéric Bibeau, Kim R. Geisinger, Rhonda K. Yantiss, Xianyong Gui, Robert F. Bradley, Massimo Milione, Joseph Misdraji, Pathology, Basingstoke and North Hampshire Foundation Trust, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), The Royal London Hospital, Department of Pathology, Wake Forest Univ./Medicine Medical Center, University of Calgary, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), IRCCS Istituto Nazionale dei Tumori [Milano], Massachusetts General Hospital [Boston], University College of London [London] (UCL), The Institute for Genomic Research (TIGR), Erasmus University Rotterdam, and Weill Medical College of Cornell University [New York]
Subjects: Adenoma, Pathology, medicine.medical_specialty, Histology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Appendix, Pathology and Forensic Medicine, Diagnosis, Differential, 03 medical and health sciences, Peritoneal Neoplasm, 0302 clinical medicine, Polyps, medicine, Pseudomyxoma peritonei, Humans, Peritoneal Neoplasms, Vermiform, business.industry, General Medicine, medicine.disease, Pseudomyxoma Peritonei, digestive system diseases, 3. Good health, Appendiceal neoplasms, medicine.anatomical_structure, Appendiceal Neoplasms, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Differential diagnosis, Peritoneum, business
Abstract: International audience; The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.
Published: 2017

19. Aberrant granulosa cell-fate related to inactivated p53/Rb signaling contributes to granulosa cell tumors and to FOXL2 downregulation in the mouse ovary

Author: Nathalie di Clemente, Catherine Genestie, Charlotte M. François, Victoria Cluzet, Florence Petit, Frank Giton, Marie M Devillers, Joëlle Cohen-Tannoudji, Celine J. Guigon, Stéphanie Chauvin, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, EXPRESSION, Forkhead Box Protein L2, Cancer Research, endocrine system, Tumor suppressor gene, Ovarian Granulosa Cell, Carcinogenesis, Granulosa cell, ANTI-MULLERIAN HORMONE, [SDV]Life Sciences [q-bio], INHIBITION, PROTEIN, Down-Regulation, Mice, Transgenic, Tumor initiation, medicine.disease_cause, Retinoblastoma Protein, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, Genetics, medicine, E2F1, Animals, Humans, Molecular Biology, Cells, Cultured, Granulosa Cell Tumor, Granulosa Cells, biology, RECEPTOR, MUTATIONS, PROLIFERATION, Anti-Müllerian hormone, FOLLICULAR DEVELOPMENT, LOCALIZATION, GENE, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, Tumor Suppressor Protein p53
Abstract: International audience; Ovarian granulosa cell tumors (GCTs) are indolent tumors of the ovary affecting women at all ages and potentially displaying late recurrence. Even if there is still little information regarding the mechanisms involved in GCT development and progression, FOXL2 would be a major tumor suppressor gene in granulosa cells. We analyzed the mechanisms underlying GCT initiation and progression by using mice with targeted expression of SV40 large T-antigen in granulosa cells (AT mouse), which develop GCTs. Consistent with patients, AT mice with developing GCTs displayed increased levels in circulating anti-Mullerian hormone (AMH), estradiol and androgens, as well as decreased FOXL2 protein abundance. Very few mice developed metastases (1 out of 30). In situ analyses revealed that GCT initiation resulted from both increased granulosa cell survival and proliferation in large antral follicles. Tumorigenesis was associated with the combined inactivation of p53 and Rb pathways, as shown by the impaired expression of respective downstream targets regulating cell apoptosis and proliferation, i.e., Bax, Bak, Gadd45a, Ccna2, Ccne1, E2f1, and Orc1. Importantly, the expression of FOXL2 was still present in newly developed GCTs and its downregulation only started during GCT growth. Collectively, our experiments provide evidence that disrupted p53/Rb signaling can drive tumor initiation and growth. This model challenges the current paradigm that impaired FOXL2 signaling is a major switch of granulosa cell tumorigenesis, albeit possibly contributing to tumor growth.
Published: 2019

20. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

Author: Richard Delarue, Emmanuelle Nicolas-Virelizier, Reda Bouabdallah, Veronique Edeline, Bertrand Joly, Adrian Tempescul, Hassan Farhat, Luc-Matthieu Fornecker, Peggy Dartigues, René-Olivier Casasnovas, Laurent Martin, Franck Morschhauser, Aspasia Stamatoullas, Pauline Brice, Marc André, Alain Delmer, Michel Meignan, Nicolas Mounier, Hervé Ghesquières, Jehan Dupuis, Philippe Quittet, Krimo Bouabdallah, Julien Lazarovici, Alina Berriolo-Riedinger, Anne-Claire Gac, Alexandra Traverse-Glehen, Pierre Feugier, Thierry Lamy, Thomas Gastinne, Hervé Maisonneuve, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Henri Mondor, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Sud Francilien, CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Département de biologie et pathologie médicales [Gustave Roussy], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Nice (CHU Nice), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Dijon, Département d'Hematologie, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CRLCC Henri Becquerel, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie [Nantes], Hôpital Sud-Fancilien, CH Sud-Fancilien, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie Hôpital Mignot, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CH La Roche-sur-Yon, Service d’Hématologie Clinique [CHU Pontchaillou, Rennes], Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dinant-Godinne UCL Namur, Service de cancérologie, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [Créteil], Université Grenoble Alpes (UGA), Département Hématologie (FNCLCC), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Régional d'Etudes sur le CANcer (GRECAN), IFR146-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse )-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département d'Hématologie Clinique [CHU Nantes], Université Mohamed Boudiaf de M'sila, Service d’Hématologie Clinique [CHRU Nancy], Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre hospitalier La Roche-Sur-Yon, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologie morphologique, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Pathologie [CHU de Dijon], Service de Médecine Interne Clermont Ferrand (MéDECINE INTERNE - CLERMONT-FERRAND), Hopital, Hôpital Archet 2 [Nice] (CHU), Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CH Evry-Corbeil, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CCSD, Accord Elsevier, Service d'Hématologie Clinique (CHU de Dijon), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’Hématologie [Rouen], CHU Rouen, Service hématologie Créteil, CHU, Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Département de médecine nucléaire (Institut Curie, Saint-Cloud), Institut Curie [Paris], Hématologie clinique [CH La Roche-sur-Yon], service hématologie Strasbourg, CHU Strasbourg, Service d’Hématologie Clinique [Rennes], Service hématologie Nice, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, CHU Henri Mondor [Créteil], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Male, medicine.medical_specialty, Vincristine, Dacarbazine, [SDV]Life Sciences [q-bio], Salvage therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Procarbazine, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, business.industry, Standard treatment, medicine.disease, Hodgkin Disease, 3. Good health, Vinblastine, Drug Therapy, Computer-Assisted, [SDV] Life Sciences [q-bio], Oncology, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: International audience; Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (
Published: 2019

21. MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib

Author: Patrick Brest, Pascal Barbry, Marius Ilie, Paul Hofman, Sandra Lassalle, Elodie Long, Frédérique Tissier, Joséphine Zangari, Philippe Vielh, Géraldine Lemaire, Imène Sarah Henaoui, Catherine Butori, Alexandra Popa, Olivier Blanck, Christelle Bonnetaud, Hélène Trouette, Nicolas Guevara, Olivier Bordone, Alexandre Bozec, Bernard Mari, Geneviève Belléannée, J.-L. Sadoul, José Santini, Isabelle Peyrottes, Bogdan Catargi, Véronique Hofman, Martine Patey, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut de la physique de la matière condensée (IPMC), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratory of Clinical and Experimental Pathology, Laboratoire d’anatomie et cytologie pathologique, Hôpital Robert Debré, CHU de Reims, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Department of Pathology, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Service d'Endocrinologie (NICE - Endocrino), Hôpital Pasteur [Nice] (CHU), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bayer Cropscience, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Infection bactérienne, inflammation, et carcinogenèse digestive, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Brest, Patrick
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Vesicular Transport Proteins, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Vandetanib, 0302 clinical medicine, Piperidines, RNA interference, medullary thyroid carcinoma, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, microRNA, treatment, Thyroid, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Immunohistochemistry, Female, RNA Interference, Research Paper, medicine.drug, Adult, vandetanib, microRNA-375, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Line, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biomarkers, Tumor, medicine, Humans, Gene silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Thyroid Neoplasms, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Cell Proliferation, business.industry, Cell growth, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Carcinoma, Neuroendocrine, Gene expression profiling, MicroRNAs, 030104 developmental biology, Quinazolines, Cancer research, business
Abstract: In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib. Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.
Published: 2016

22. Preclinical ex vivo evaluation of the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses

Author: Richard Berry, Philippe Vielh, Suzette Delaloge, René Farcy, Lama Alchab, Corinne Balleyguier, Helene Moniz-Koum, Pierre Validire, Marie-Pierre Fontaine-Aupart, Pauline Beaumel, Marie-Christine Mathieu, Alexis Toullec, Yves Vincent, Charlotte Benoit, Pierre Maroun, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Nodea Medical, Nodea Medica, Dpt pathologie, Institut Mutualiste de Montsouris (IMM), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Laboratoire de recherche translationnelle, Direction de la recherche [Gustave Roussy], Laboratoire Aimé Cotton (LAC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-École normale supérieure - Cachan (ENS Cachan), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Département de médecine oncologique [Gustave Roussy], Bases fondamentales et stratégies nouvelles en cancérologie (BFSNC - IFR54), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie diagnostique (radiologie / échographie), Département d'imagerie médicale [Gustave Roussy], and École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, In situ, medicine.medical_specialty, Adolescent, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biopsy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Breast Neoplasms, Mastectomy, Segmental, Sensitivity and Specificity, 01 natural sciences, Diagnosis, Differential, 010309 optics, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 0103 physical sciences, medicine, Humans, Radiology, Nuclear Medicine and imaging, Spectral analysis, Prospective Studies, Mastectomy, ComputingMilieux_MISCELLANEOUS, Aged, Neuroradiology, Aged, 80 and over, business.industry, Optical Imaging, Ultrasound, Lumpectomy, Equipment Design, General Medicine, Middle Aged, Fluorescence, 030220 oncology & carcinogenesis, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, business, Algorithms, Ex vivo
Abstract: To assess the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses in freshly removed surgical specimens, in preparation for its clinical development. Sixty-four breast masses from consenting patients who had undergone either a lumpectomy or a mastectomy were included. Label-free fluorescence spectral acquisitions were obtained with a 25G fibre-containing needle inserted into the mass. Data from benign and malignant masses were compared to establish the most discriminating thresholds and measurement algorithms. Accuracy was verified using the bootstrap method. The final histological examination revealed 44 invasive carcinomas and 20 benign lesions. The maximum intensity of fluorescence signal was discriminant between benign and malignant masses (p < .0001) whatever their sizes. Statistical analysis indicated that choosing five random measurements per mass was the best compromise to obtain high sensitivity and high negative predictive value with the fewest measurements. Thus, malignant tumours were identified with a mean sensitivity, specificity, negative and positive predictive value of 98.8%, 85.4%, 97.2% and 93.5%, respectively. This new in situ tissue autofluorescence evaluation device allows accurate discrimination between benign and malignant breast masses and deserves clinical development. • A new device allows in situ label-free fluorescence analysis of ex vivo breast masses • Maximum fluorescence intensity discriminates benign from malignant masses (p < .0001) • Five random measurements allow a high negative predictive value (97.2%)
Published: 2018

23. 25 gauge fibered-needle for label-free fluorescence analysis of breast masses: a first in vivo study

Author: Marie-Christine Mathieu, Christophe Tourasse, Charlotte Benoit, Marie-Pierre Fontaine-Aupart, Suzette Delaloge, Corinne Balleyguier, René Farcy, Alexis Toullec, Martine Boisserie-Lacroix, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Imagerie diagnostique (radiologie / échographie), Département d'imagerie médicale [Gustave Roussy], Nodea Medical, Nodea Medica, Centre Régional de Lutte Contre le Cancer Bergognié, Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Aimé Cotton (LAC), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Pathologie mammaire, Service de Radiologie Adultes, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital privé Jean Mermoz, and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-École normale supérieure - Cachan (ENS Cachan)
Subjects: business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Fibered knot, Gauge (firearms), Fluorescence, 030218 nuclear medicine & medical imaging, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, In vivo, 030220 oncology & carcinogenesis, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, ComputingMilieux_MISCELLANEOUS, Label free
Abstract: International audience
Published: 2018

24. Les points chauds de l’actualité en 2017. Une sélection du comité de rédaction du Bulletin du Cancer

Author: Daniel Orbach, Marie Wislez, Magali Lacroix, Manuel Rodrigues, Jean-Jacques Mazeron, Thierry André, Christophe Massard, Nicolas Magné, Jacques-Olivier Bay, Christophe Caux, Carole Bouleuc, Stéphane Vignot, Anthony Gonçalves, Serge Evrard, Gilles L'Allemain, Juliette Thariat, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Head of Digestive Tumours Unit and Department of Surgery, Université Bordeaux Segalen - Bordeaux 2, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie [Paris], ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Nice Sophia Antipolis (1965 - 2019) (UNS), CHU Tenon [APHP], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Mines de St Etienne, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Service de Radiothérapie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Curie, ONERA, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), and Université Clermont Auvergne (UCA)
Subjects: Cancer Research, Library science, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, Editorial board, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Political science, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, health care economics and organizations, ComputingMilieux_MISCELLANEOUS
Abstract: Actuality was dense in 2017 for oncology and hematology. The editorial board of the Bulletin du Cancer proposes a selection of key data distinguishing four trends: precision medicine, immunotherapy, focus on early stages and global management of metastatic disease. A summary of results which have been published or presented in congresses is proposed and the impact on daily practices is discussed.
Published: 2018

25. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association

Author: Sarkozy , Clémentine, Molina , Thierry, Ghesquières , Hervé, Michallet , Anne-Sophie, Dupuis , Jehan, Damotte , Diane, Morsschauser , Franck, Parrens , Marie, Laurent , Laurent, Dartigues , Peggy, Stamatoullas , Aspasia, Hirsch , Pierre, Fabiani , Bettina, Bouabdallah , Krimo, da Silva , Maria Gomes, Maerevoet , Marie, Laurent , Camille, Coiffier , Bertrand, Salles , Gilles, Traverse-Glehen , Alexandra, Sarkozy , Pierre, Ghesquières , Pierre, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Léon Bérard [Lyon], École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Bordeaux [Bordeaux], Aix-Marseille Université - Faculté d'odontologie ( AMU ODONTO ), Aix Marseille Université ( AMU ), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), CRLCC Henri Becquerel, Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Mohamed Boudiaf de M'sila, Institut Jules Bordet, Departement de Pathologie, Institut Claudius Regaud,Toulouse, Fédération Nationale des Centres de Lutte contre le Cancer, Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, and Hospices Civils de Lyon ( HCL )
Subjects: immune system diseases, hemic and lymphatic diseases, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract: International audience; Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalated BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
Published: 2017

26. Diagnosis of HPV driven oropharyngeal cancers: Comparing p16 based algorithms with the RNAscope HPV-test

Author: Antoine E. Melkane, Isabelle Borget, Philippe Vielh, Yuling Luo, Joanne Guerlain, Céline Mourareau, Aïcha Ben Lakdhar, Jean-Yves Scoazec, Xiao-Jun Ma, Françoise Drusch, Lacau St Guily, Haitham Mirghani, Ming-Xiao He, Anne Auperin, Cécile Badoual, Furrat Amen, Véronique Dalstein, Odile Casiraghi, LPP - Laboratoire de Phonétique et Phonologie - UMR 7018 (LPP), Université Sorbonne Nouvelle - Paris 3-Centre National de la Recherche Scientifique (CNRS), Service d’Otorhino-laryngologie et de chirurgie cervicofaciale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de recherche translationnelle, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Reims Champagne-Ardenne (URCA), and Pathologie morphologique
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, [SDV]Life Sciences [q-bio], Biology, Alphapapillomavirus, Single test, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Routine clinical practice, Hpv test, ComputingMilieux_MISCELLANEOUS, In Situ Hybridization, P16 immunohistochemistry, Head and neck cancer, Cancer, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Oropharyngeal Neoplasms, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Oral Surgery, Algorithm, Oropharyngeal Cancers, Algorithms
Abstract: Background Accurate identification of HPV-driven oropharyngeal cancer (OPC) is a major issue and none of the current diagnostic approaches is ideal. An in situ hybridization (ISH) assay that detects high-risk HPV E6/E7 mRNA, called the RNAscope HPV-test, has been recently developed. Studies have suggested that this assay may become a standard to define HPV-status. Methods To further assess this test, we compared its performance against the strategies that are used in routine clinical practice: p16 immunohistochemistry (IHC) as a single test and algorithms combining p16-IHC with HPV-DNA identification by PCR (algorithm-1) or ISH (algorithm-2). Results 105 OPC specimens were analyzed. The prevalence of HPV-positive samples varied considerably: 67% for p16-IHC, 54% for algorithm-1, 61% for algorithm-2 and 59% for the RNAscope HPV-test. Discrepancies between the RNAscope HPV-test and p16-IHC, algorithm-1 and 2 were noted in respectively 13.3%, 13.1%, and 8.6%. The 4 diagnostic strategies were able to identify 2 groups with different prognosis according to HPV-status, as expected. However, the greater survival differential was observed with the RNAscope HPV-test [HR: 0.19, 95% confidence interval (CI), 0.07–0.51, p = 0.001] closely followed by algorithm-1 (HR: 0.23, 95% CI, 0.08–0.66, p = 0.006) and algorithm-2 (HR: 0.26, 95% CI, 0.1–0.65, p = 0.004). In contrast, a weaker association was found when p16-IHC was used as a single test (HR: 0.33, 95% CI, 0.13–0.81, p = 0.02). Conclusions Our findings suggest that the RNAscope HPV-test and p16-based algorithms perform better that p16 alone to identify OPC that are truly driven by HPV-infection. The RNAscope HPV-test has the advantage of being a single test.
Published: 2016

27. Management of desmoid tumours: A nationwide survey of labelled reference centre networks in France

Author: Yves-Marie Robin, G. Ferron, Axel Le Cesne, Jean-Yves Blay, Nicolas Isambert, Florence Duffaud, Agnès Neuville, Isabelle Ray-Coquard, Cécile Le Péchoux, C. Guillemet, François Bertucci, Eberhad Stoeckle, Dominique Ranchère-Vince, Philippe Terrier, Maria Rios, Nicolas Penel, Jean-Michel Coindre, J.B. Courrèges, Sylvie Bonvalot, Antoine Italiano, Santé publique : épidémiologie et qualité des soins-EA 2694 ( CERIM ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Oscar Lambret, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Institut Gustave Roussy ( IGR ), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Department of Surgical Oncology Institut Claudius Regaud, Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Département de médecine oncologique [Gustave Roussy], Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de radiothérapie [Gustave Roussy], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER, and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Pathology, Cancer Research, Time Factors, Databases, Factual, analysis, diagnosis, Biopsy, DNA Mutational Analysis, Nationwide survey, Medical Oncology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, surgery, 0302 clinical medicine, Mutational status, Cooperative Behavior, Child, Referral and Consultation, Early Detection of Cancer, beta Catenin, Aged, 80 and over, Delivery of Health Care, Integrated, Incidence (epidemiology), Incidence, Middle Aged, Quality Improvement, Optimal management, 3. Good health, Fibromatosis, Aggressive, Phenotype, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Rare tumours, Desmoid tumours, Female, France, Adult, medicine.medical_specialty, Referral, Adolescent, Patients, [SDV.CAN]Life Sciences [q-bio]/Cancer, Time-to-Treatment, methods, Time, Key indicators of activity, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Expert network, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, radiotherapy, Aged, Quality Indicators, Health Care, Patient Care Team, Reference centres, business.industry, General surgery, Public health, 030104 developmental biology, Clinical diagnosis, Health Care Surveys, Mutation, pathology, Biopsy, Large-Core Needle, business, Program Evaluation
Abstract: International audience; PURPOSE: The optimal management of rare tumours (i.e. from accurate diagnosis to management in reference centres) is a public health challenge. In 2009, the French National Cancer Institute (INCa) identified and financially supported the two expert networks for pathological and clinical diagnosis and management of soft tissue tumours. METHODS: The activities of both networks were prospectively collected using a nationwide database (rreps.org). Data describing the diagnosis management of 863 successive cases of desmoids tumours (DT) were prospectively collected from 2010 to 2013 and analysed. RESULTS: The number of confirmed DT constantly improved from January 2010 to December 2013 (from 173 to 273 cases per year); the expected incidence ranged from 132 to 330 cases/year. The rate of cases diagnosed with core-needle biopsies and CTNNB1 mutational status analysis increased from 30.6 to 40.7% and from 87.8 to 94.1%, respectively. The mean delay for pathological diagnosis confirmation constantly decreased from 107 to 47 d. Among the 846 adult patients, 414 (48.9%) patients were treated by reference centres. The rate of patients managed by reference centres constantly increased with time from 36.9 to 49.5% since 2010. The median management time of the referral centres constantly decreased from 440 to 67 d. CONCLUSION: The two expert networks worked synergistically and improved diagnosis modalities of rare desmoid tumours at a national level. The impact of management by expert networks on the outcome will be prospectively analysed in the future
Published: 2016

28. Underlining the complexity of the structural and chemical characteristics of ectopic calcifications in breast tissues through FE-SEM and μFTIR spectroscopy

Author: Michel Daudon, Dominique Bazin, Alex Kellum, Corinne Balleyguier, Aïcha Ben Lakhdar, Marie-Christine Mathieu, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clemson University, Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: In situ, Materials science, Micrometer scale, Chemistry(all), General Chemical Engineering, 030232 urology & nephrology, Analytical chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apatite, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Nuclear magnetic resonance, breast cancer, medicine, Spectroscopy, skin and connective tissue diseases, [PHYS]Physics [physics], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Field emission scanning electron microscopy, micro Fourier Transform Infrared spectroscopy, General Chemistry, medicine.disease, 3. Good health, Carbonate level, calcifications, Carbonated calcium phosphate, 030220 oncology & carcinogenesis, visual_art, visual_art.visual_art_medium, Chemical Engineering(all), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Breast calcifications, defined as calcium deposits within breast tissue, can arise from a vast number of aetiologies. Diffuse or scattered distribution is typically seen in benign entities. Approximately 95% of all Ductal carcinoma-in-situ, which represents 25–30% of all reported breast cancers are diagnosed because of mammographically detected microcalcifications. In this investigation dedicated to breast calcifications, we assessed at the micrometer scale their chemical nature through last generation micro-Fourier transform Infrared microspectroscopy and their structural characteristics through last generation field emission scanning electron microscopy. Several striking results have been obtained. Heavily mineralized deposits seem to be the result of the agglomeration of micrometer scale spherules and for the first time, we show that micrometer scale spherules display very different internal structure. Moreover, while Ca phosphate apatite and calcium oxalate dihydrate are the two chemical phases usually reported, we underline the presence of a third chemical phase namely amorphous carbonated calcium phosphate. In the case of duct carcinoma in situ (DCIS), the chemical composition as well as the carbonate level are very inhomogeneous even inside micrometer scale breast calcifications. Moreover, for some samples related to DCIS, special features at the micrometer scale seem to be related to this pathology because they were not found for the other pathologies.
Published: 2016

29. First Observation of Leptospira interrogans in the Lungs of Rattus norvegicus

Author: Zoheira Djelouadji, Anne-Laure Zilber, Marc Artois, Patrick Belli, Angeli Kodjo, UMR 1233 MTCX Mycotoxines et Toxicologie Comparée des Xénobiotiques, Institut National de la Recherche Agronomique (INRA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université de Lyon, Mycotoxines et Toxicologie Comparée des Xénobiotiques (MET), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Lyon (ENVL), UP Pathologie Morphologique et Clinique, Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233 (RS2GP), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire des Leptospires, Klaus P. Hunfeld, Zilber, Anne-Laure, and Ecole Nationale Vétérinaire de Lyon (ENVL)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Serotype, Article Subject, [SDV]Life Sciences [q-bio], animal diseases, 030231 tropical medicine, 030106 microbiology, lcsh:Medicine, Kidney, General Biochemistry, Genetics and Molecular Biology, Serology, 03 medical and health sciences, 0302 clinical medicine, Blood serum, Leptospira, RNA, Ribosomal, 16S, medicine, Animals, Humans, Leptospirosis, Typing, Lung, General Immunology and Microbiology, biology, lcsh:R, General Medicine, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Virology, 3. Good health, Rats, medicine.anatomical_structure, bacteria, Leptospira interrogans, Research Article
Abstract: We report the first two cases of pulmonary presence of leptospires in apparently healthy rats captured in a city park in Lyon (France). Only renal carriage ofLeptospirahas been described in the literature. Blood serology was performed in parallel with molecular and histological analyses of the kidney and lung samples. We isolated leptospires from the kidneys of two out of three seropositive wild rats. These results were confirmed by specific detection of pathogenicLeptospiraby real-time PCR. Moreover,LeptospiraDNA was detected in lung tissues. Immunohistochemistry and Warthin-Starry staining revealed that leptospires were present on the surface of the ciliated epithelium of the bronchi. Using PCR of therrs(16S) gene and Multispacer Sequence Typing, DNA extracts of the kidney and lung were identified as belonging toLeptospira interrogansserovar Icterohaemorrhagiae “CHU Réunion.” This first observation of the presenceLeptospirain the lung with simultaneous renal carriage will require further study in future on several target organs to gain a better understanding of theLeptospirainfection in wild rat.
Published: 2016
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30. Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?

Author: Céline Loubatier, Nicolas Guevara, Marius Ilie, Abir Al Ghuzlan, Géraldine Rios, Christelle Bonnetaud, Kevin Lebrigand, Véronique Hofman, Sandra Lassalle, Marie-Pierre Puissegur, Philippe Vielh, Bruno Cardinaud, Olivier Bordone, Bernard Mari, J. Santini, Pascal Barbry, Patrick Brest, Brigitte Franc, Paul Hofman, Infection bactérienne, inflammation, et carcinogenèse digestive, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Laboratoire de Pathologie Clinique et Expérimentale, Centre Hospitalier Universitaire de Nice (CHU Nice), Human Tissue Biobank Unit, Hôpital Pasteur [Nice] (CHU), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Dept. of Oto-Rhino-Laryngology, Department of Pathology, Hôpital Ambroise Paré [AP-HP], Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Laboratoire de recherche translationnelle (Labo RT), Immunologie des tumeurs et immunothérapie (UMR 1015), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Cancer Research, Pathology, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Thyroid Gland, Immunoenzyme Techniques, 0302 clinical medicine, Endocrinology, Adenocarcinoma, Follicular, RNA, Neoplasm, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Benignity, Thyroid, Cell Differentiation, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Biology, Real-Time Polymerase Chain Reaction, Malignancy, Thyroid carcinoma, Young Adult, 03 medical and health sciences, Biomarkers, Tumor, medicine, Carcinoma, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Thyroid Neoplasms, Aged, 030304 developmental biology, Gene Expression Profiling, medicine.disease, Carcinoma, Papillary, Gene expression profiling, MicroRNAs, Mutation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The term ‘thyroid tumors of uncertain malignant potential’ (TT-UMP) was coined by surgical pathologists to define well-differentiated tumors (WDT) showing inconclusive morphological evidence of malignancy or benignity. We have analyzed the expression of microRNA (miRNA) in a training set of 42 WDT of different histological subtypes: seven follicular tumors of UMP (FT-UMP), six WDT-UMP, seven follicular thyroid adenomas (FTA), 11 conventional papillary thyroid carcinomas (C-PTC), five follicular variants of PTC (FV-PTC), and six follicular thyroid carcinomas (FTC), which led to the identification of about 40 deregulated miRNAs. A subset of these altered miRNAs was independently validated by qRT-PCR, which included 18 supplementary TT-UMP (eight WDT-UMP and ten FT-UMP). Supervised clustering techniques were used to predict the first 42 samples. Based on the four possible outcomes (FTA, C-PTC, FV-PTC, and FTC), about 80% of FTA and C-PTC and 50% of FV-PTC and FTC samples were correctly assigned. Analysis of the independent set of 18 WDT-UMP by quantitative RT-PCR for the selection of the six most discriminating miRNAs was unable to separate FT-UMP from WDT-UMP, suggesting that the miRNA signature is insufficient in characterizing these two clinical entities. We conclude that considering FT-UMP and WDT-UMP as distinct and specific clinical entities may improve the diagnosis of WDT of the thyroid gland. In this context, a small set of miRNAs (i.e.miR-7,miR-146a,miR-146b,miR-200b,miR-221, andmiR-222) appears to be useful, though not sufficientper se, in distinguishing TT-UMP from other WDT of the thyroid gland.
Published: 2011
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31. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

Author: Bertolotto-Ballotti, Corine, Lesueur, Fabienne, Giuliano, Sandy, Strub, Thomas, de Lichy, Mahaut, Bille, Karine, Dessen, Philippe, d'Hayer, Benoit, Mohamdi, Hamida, Remenieras, Audrey, Maubec, Eve, de La Fouchardière, Arnaud, Molinié, Vincent, Vabres, Pierre, Dalle, Stéphane, Poulalhon, Nicolas, Martin-Denavit, Tanguy, Thomas, Luc, Andry-Benzaquen, Pascale, Dupin, Nicolas, Boitier, Françoise, Rossi, Annick, Perrot, Jean-Luc, Labeille, Bruno, Robert, Caroline, Escudier, Bernard, Caron, Olivier, Brugières, Laurence, Saule, Simon, Gardie, Betty, Gad, Sophie, Richard, Stéphane, Couturier, Jérôme, Teh, Bin Tean, Ghiorzo, Paola, Pastorino, Lorenza, Puig, Susana, Badenas, Celia, Olsson, Hakan, Ingvar, Christian, Rouleau, Etienne, Lidereau, Rosette, Bahadoran, Philippe, Vielh, Philippe, Corda, Eve, Blanché, Hélène, Zelenika, Diana, Galan, Pilar, Renseigné, Non, Aubin, François, Bachollet, Bertrand, Becuwe, Céline, Berthet, Pascaline, Bignon, yves Jean, Bonadona, Valérie, Bonafe, Jean-Louis, Bonnet-Dupeyron, Marie-Noëlle, Cambazard, Fréderic, Chevrant-Breton, Jacqueline, Coupier, Isabelle, Dalac, Sophie, Demange, Liliane, d'Incan, Michel, Dugast, Catherine, Faivre, Laurence, Vincent-Fétita, Lynda, Gauthier-Villars, Marion, Gilbert, Brigitte, Grange, Florent, Grob, Jean-Jacques, Humbert, Philippe, Janin, Nicolas, Joly, Pascal, Kerob, Delphine, Lasset, Christine, Leroux, Dominique, Levang, Julien, Limacher, Jean-Marc, Livideanu, Cristina, Longy, Michel, Lortholary, Alain, Stoppa-Lyonnet, Dominique, Mansard, Sandrine, Mansuy, Ludovic, Marrou, Karine, Matéus, Christine, Maugard, Christine, Meyer, Nicolas, Nogues, Catherine, Souteyrand, Pierre, Venat-Bouvet, Laurence, Zattara, Hélène, Chaudru, Valérie, Lenoir, Gilbert M, Lathrop, Mark, Davidson, Irwin, Avril, Marie-Françoise, Demenais, Florence, Ballotti, Robert, Bressac-de Paillerets, Brigitte, Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), AxesSim, Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomopathologie [Fort de France, Martinique], CHU Fort de France, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Parallel Cooperative Multi-criteria Optimization (DOLPHIN), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Valorisation Recherche et Innovations Alimentaire (Valorial), University Hospital of St-Etienne, Department of Dermatology, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'immunothérapie, Institut Gustave Roussy (IGR), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Immunologie des Tumeurs Humaines (U753), Laboratoire de Génétique Oncologique [Villejuif], École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, Service de Génétique Oncologique, Institut Curie, Van Andel Research Institute, Grand Rapids, Michigan, Van Andel Institute [Grand Rapids], University of Barcelona, Hospital Clinic Barcelona, Lund University [Lund], Department of Surgery, Clinical Sciences, Genetique Moleculaire des Cancers d'Origine Epitheliale, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel - EA 3886), Université d'Évry-Val-d'Essonne (UEVE), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditérannéen de médecine moléculaire (C3M), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Apoptose, cancer et immunité (U848), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'anatomie pathologique, Hôpital Saint Joseph, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Consultation de génétique, Département de Pédiatrie, Service de Pathologie, Institut Curie [Paris], Department of Oncology, Clinical Sciences, Department of Cancer Epidemiology, Clinical Sciences, Department of Surgery, University Hospital of Lund, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Hôpital René HUGUENIN (Saint-Cloud), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de génétique Epidémiologique, Centre Léon Bérard [Lyon], CHU Saint-Etienne, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Polyclinique de Courlancy, Service de Dermatologie, Hôtel-Dieu, CRLCC Eugène Marquis (CRLCC), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM), Département de Génétique, CHU, Liège, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology, Service d'onco-hématologie et génétique, CHU Grenoble, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de diagnostic génétique, Hôpital Universitaire de Strasbourg, Strasbourg, Laboratoire de biostatistique, CHU Strasbourg, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Département de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Functional Genomics and Cancer, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7), We thank the patients and family members who participated in this study and the clinicians who identified these families, the French Familial Melanoma Study Group and the Inherited Predisposition to Kidney Cancer network. We acknowledge the contribution of the IGR Biobank for providing MELARISK samples and the CEPH Biobank for processing DNA samples. We thank L. Larue, J, Feunteun, A. Sarasin and E. Solary for critical reviews of the manuscript. We thank V. Lazar and S. Forget for coordination of the IGR's genomics and genetic platforms, N. Pata-Merci, V. Marty, S. Le Gras and A. Chabrier for their technical expertise, and M. Barrois for technical counselling. We also thank A. Boland for DNA extraction and quality control for genome-wide genotyping. This work was supported by grants from INSERM, Ligue Nationale Contre Le Cancer (PRE05/FD and PRE 09/FD) to F. D., Programme Hospitalier de Recherche Clinique (PHRC 2007/AOM-07-195) to M.-F.A. and F. D., ARC NoA09/5/5003 to B.B.-d.P., ARC 4985 to C. B., Institut National du Cancer (INCa)-Canceropole Ile de France (melanoma network RS#13) to B.B.-deP., INCa-PNES rein to B. G., S.Ga. and S. R., INCa grant R08009AP to C. B., Fondation de France 2010 to R. B., INCa and Ligue National Contre le Cancer to I. D., Fond de maturation IGR and Fondation Gustave Roussy to B.B.-d.P., Societe Francaise de Dermatologie SDF2004 to R. B. and P. B., SFD2009 to B.B.-d.P., 2009 SGR 1337 from AGAUR, Generalitat de Catalunya, and FIS PS09/01393 from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain to S. P. and C. B., and personal donations from C. and N. de Paillerets and M.-H.Wagner. to B.B.-d.P. B.B-d.P. holds an INSERM Research Fellowship for hospital-based scientists. Work at the Centre National de Genotypage (CNG) and Centre d'Etude du Polymorphisme Humain (CEPH) was supported in part by INCa., Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -IFR50-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Génétique, Institut de cancérologie Gustave Roussy, Villejuif, France, Institut Gustave Roussy ( IGR ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Laboratoire Electronique, Informatique et Image [UMR6303] ( Le2i ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-École Nationale Supérieure d'Arts et Métiers ( ENSAM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), INSTITUT CURIE, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), Centre François Baclesse, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, CRLCC Eugène Marquis ( CRLCC ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP), Validation et identification de nouvelles cibles en oncologie ( VINCO ), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: multidisciplinary sciences, MESH : Germ-Line Mutation, SUMO protein, urologic and male genital diseases, medicine.disease_cause, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, Gene Frequency, Cell Movement, MESH: Germ-Line Mutation, MESH : Cell Movement, MESH : Gene Frequency, MESH: Cell Movement, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Multidisciplinary, MESH: Sumoylation, Melanoma, MESH : Sumoylation, MESH: Genetic Predisposition to Disease, renal carcinoma, MESH: Carcinoma, Renal Cell, Microphthalmia-associated transcription factor, MESH : Microphthalmia-Associated Transcription Factor, 3. Good health, germline mutation, 030220 oncology & carcinogenesis, MESH: Microphthalmia-Associated Transcription Factor, science and technology, MESH: Melanoma, sumo, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Germline mutation, melanoma, MESH: Gene Frequency, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Neoplasm Invasiveness, Carcinoma, Renal Cell, neoplasms, Transcription factor, Germ-Line Mutation, 030304 developmental biology, Microphthalmia-Associated Transcription Factor, MESH: Humans, MESH : Humans, Sumoylation, MESH: Neoplasm Invasiveness, medicine.disease, HIF1A, cancer cells, Cancer research, MESH : Genetic Predisposition to Disease, Carcinogenesis
Abstract: International audience; So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
Published: 2011

32. Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma

Author: Min-Han Tan, Jun Sugimura, Jonathon A. Ditlev, Annick Vieillefond, Tomoaki Fujioka, Puay Hoon Tan, Ximing J. Yang, Daisuke Matsuda, Delphine Amsellem-Ouazana, Eric J. Kort, Nicolas Thiounn, Chin Fong Wong, Sophie Giraud, Philippe Vielh, Thierry Flam, Bin Tean Teh, Bernard Debré, Stéphane Richard, Sophie Ferlicot, Marc Zerbib, Kyle A. Furge, Sok Kean Khoo, Hwei Ling Tan, Gérard Benoit, Vincent Molinié, Stéphane Droupy, BMC, Ed., Laboratory of Cancer Genetics, Van Andel Institute [Grand Rapids], NCCS-VARI Translational Cancer Research Laboratory, National Cancer Centre Singapore, Department of Medical Oncology, Department of Epidemiology and Public Health, National University of Singapore (NUS), Department of Pathology, Singapore General Hospital, Northwestern University Feinberg School of Medicine, Department of Urology, Iwate Medical University School of Medicine, Laboratory of Computational Biology, Laboratory of Molecular Epidemiology, Laboratoire de Génétique, Hôpital Herriot, Laboratoire d'Anatomie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de Bicêtre, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'urologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie pathologique, Hôpital Saint Joseph, Laboratoire d'anatomie pathologique, Consultation d'oncogénétique spécialisée, Hôpital de Bicêtre-Service d'Urologie, and We wish to thank the Fischer Family Foundation, the Singapore Cancer Society, the French National Cancer Institute (Kidney PNES, INCa), and the French League against Cancer (Comités du Cher et de l'Indre) for supporting this study. We would also like to thank the Hauenstein Foundation and the Van Andel Foundation for their continued support. We thank the Cooperative Human Tissue Network (CHTN) of the National Cancer Institute for providing samples for analysis. Min-Han Tan is supported by the Singapore Millenium Foundation and the National Kidney Foundation.
Subjects: Pathology, Cancer Research, Chromophobe Renal Cell Carcinoma, Gene Dosage, Chromophobe cell, urologic and male genital diseases, MESH: Gene Dosage, 0302 clinical medicine, Odds Ratio, Adenoma, Oxyphilic, Oncocytoma, Gene Regulatory Networks, MESH: Nerve Tissue Proteins, Renal oncocytoma, MESH: Gene Regulatory Networks, Oligonucleotide Array Sequence Analysis, Synaptogyrins, 0303 health sciences, MESH: Genetic Testing, MESH: Polymorphism, Single Nucleotide, MESH: Carcinoma, Renal Cell, MESH: Gene Expression Regulation, Neoplastic, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, MESH: Predictive Value of Tests, Kidney Neoplasms, MESH: Reproducibility of Results, Gene Expression Regulation, Neoplastic, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Cytogenetic Analysis, MESH: Membrane Proteins, Research Article, medicine.medical_specialty, MESH: Adenoma, Oxyphilic, MESH: Chromosomes, Human, Pair 1, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nerve Tissue Proteins, Computational biology, Biology, Gene dosage, Polymorphism, Single Nucleotide, lcsh:RC254-282, Diagnosis, Differential, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Diagnosis, Differential, Predictive Value of Tests, medicine, Genetics, Biomarkers, Tumor, Humans, MESH: Tumor Suppressor Proteins, Genetic Testing, Carcinoma, Renal Cell, 030304 developmental biology, MESH: Humans, MESH: Cytogenetic Analysis, Gene Expression Profiling, Tumor Suppressor Proteins, MESH: Aquaporin 6, Membrane Proteins, Reproducibility of Results, MESH: Immunohistochemistry, Gene signature, medicine.disease, MESH: Odds Ratio, Aquaporin 6, Gene expression profiling, Clear cell renal cell carcinoma, MESH: Tumor Markers, Biological, MESH: Oligonucleotide Array Sequence Analysis, MESH: Kidney Neoplasms
Abstract: Background Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. Results A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusions Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
Published: 2010

33. Nouveautés en pathologie thyroïdienne : classification OMS 2022, système Bethesda 2023, biologie moléculaire et testing moléculaire.

Author: Bani MA, Moog S, Suciu V, Lamartina L, and Ghuzlan AA
Subjects: Humans, Molecular Biology, Thyroid Gland pathology, High-Throughput Nucleotide Sequencing, Thyroid Neoplasms genetics, Thyroid Neoplasms classification, Thyroid Neoplasms pathology, World Health Organization
Abstract: Advances in Thyroid Pathology: WHO CLASSIFICATION 2022, BETHESDA SYSTEM 2023, MOLECULAR BIOLOGY AND MOLECULAR TESTING: Thyroid pathology has experienced significant advances with the publication of the 5th edition of the World Health Organization classification of endocrine tumors in 2022 and the third edition of the Bethesda system for thyroid cytopathology in 2023. At the same time, the availability of next-generation sequencing data coupled with numerous translational research projects have considerably increased our knowledge of the genomics and mechanics of thyroid cancers, enabling us to refine prognosis and propose new targeted therapies. In this review, we will take up the main new features of the WHO 2022 and Bethesda 2023 classifications, as well as molecular biology findings, with an emphasis on the practical implications for clinicians., Competing Interests: Liens d’intérêts S. Moog, M. Amine Bani, A. Al Ghuzlan et V. Suciu déclarent ne pas avoir de liens d’intérêts. L. Lamartina déclare des liens d’intérêts pour des financements pour participation à un congrès de la part des laboratoires AAA Novartis et Ipsen; pour participation à des tumor boards de la part des laboratoires Eisai et Ipsen; pour des honoraires perçus de la part des laboratoires Eisai, Lilly et Roche. Cet article fait partie du supplément Prise en charge des cancers thyroïdiens en 2024 : avancées diagnostiques et thérapeutiques réalisé avec le soutien institutionnel de Lilly., (Copyright © 2024 Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.)
Published: 2024
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34. Organoids for Functional Precision Medicine in Advanced Pancreatic Cancer.

Author: Boilève A, Cartry J, Goudarzi N, Bedja S, Mathieu JRR, Bani MA, Nicolle R, Mouawia A, Bouyakoub R, Nicotra C, Ngo-Camus M, Job B, Lipson K, Boige V, Valéry M, Tarabay A, Dartigues P, Tselikas L, de Baere T, Italiano A, Cosconea S, Gelli M, Fernandez-de-Sevilla E, Annereau M, Malka D, Smolenschi C, Ducreux M, Hollebecque A, and Jaulin F
Subjects: Humans, Male, Female, Middle Aged, Aged, Prospective Studies, Mutation, Antineoplastic Agents therapeutic use, Aged, 80 and over, Adult, Predictive Value of Tests, Biomarkers, Tumor genetics, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality, Organoids, Precision Medicine, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal therapy
Abstract: Background & Aims: Patient-derived organoids (PDOs) are promising tumor avatars that could enable ex vivo drug tests to personalize patients' treatments in the frame of functional precision oncology. However, clinical evidence remains scarce. This study aims to evaluate whether PDOs can be implemented in clinical practice to benefit patients with advanced refractory pancreatic ductal adenocarcinoma (PDAC)., Methods: During 2021 to 2022, 87 patients were prospectively enrolled in an institutional review board-approved protocol. Inclusion criteria were histologically confirmed PDAC with the tumor site accessible. A panel of 25 approved antitumor therapies (chemogram) was tested and compared to patient responses to assess PDO predictive values and map the drug sensitivity landscape in PDAC., Results: Fifty-four PDOs were generated from 87 pretreated patients (take-on rate, 62%). The main PDO mutations were KRAS (96%), TP53 (88%), and CDKN2A/B (22%), with a 91% concordance rate with their tumor of origin. The mean turnaround time to chemogram was 6.8 weeks. In 91% of cases, ≥1 hit was identified (gemcitabine (n = 20 of 54), docetaxel (n = 18 of 54), and vinorelbine (n = 17 of 54), with a median of 3 hits/patient (range, 0-12). Our cohort included 34 evaluable patients with full clinical follow-up. We report a chemogram sensitivity of 83.3% and specificity of 92.9%. The overall response rate and progression-free survival were higher when patients received a hit treatment as compared to patients who received a nonhit drug (as part of routine management). Finally, we leveraged our PDO collection as a platform for drug validation and combo identification. We tested anti-KRAS G12D (MRTX1133), alone or combined, and identified a specific synergy with anti-EGFR therapies in KRAS G12D variants., Conclusions: We report the largest prospective study aiming at implementing PDO-based functional precision oncology and identify very robust predictive values in this clinical setting. In a clinically relevant turnaround time, we identify putative hits for 91% of patients, providing unexpected potential survival benefits in this very aggressive indication. Although this remains to be confirmed in interventional precision oncology trials, PDO collection already provides powerful opportunities for drugs and combinatorial treatment development., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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35. Direct Reprogramming of Hepatocytes Into JAK/Stat-Dependent LGR5+ Liver Cells Able to Initiate Intrahepatic Cholangiocarcinoma.

Author: Chaker D, Desterke C, Moniaux N, Bani MA, Oudrhiri N, Faivre J, Turhan AG, Bennaceur-Griscelli A, and Griscelli F
Subjects: Animals, Mice, Hepatocytes metabolism, Bile Ducts, Intrahepatic metabolism, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Wnt Signaling Pathway genetics, Cholangiocarcinoma genetics, Cholangiocarcinoma metabolism, Bile Duct Neoplasms genetics, Bile Duct Neoplasms metabolism
Abstract: Somatic cells that have been partially reprogrammed by the factors Oct4, Sox2, Klf4, and cMyc (OSKM) have been demonstrated to be potentially tumorigenic in vitro and in vivo due to the acquisition of cancer-associated genomic alterations and the absence of OSKM clearance over time. In the present study, we obtained partially reprogrammed, SSEA1-negative cells by transducing murine hepatocytes with Δ1Δ3-deleted adenoviruses that expressed the 4 OSKM factors. We observed that, under long-term 2D and 3D culture conditions, hepatocytes could be converted into LGR5-positive cells with self-renewal capacity that was dependent on 3 cross-signaling pathways: IL6/Jak/Stat3, LGR5/R-spondin, and Wnt/β-catenin. Following engraftment in syngeneic mice, LGR5-positive cells that expressed the cancer markers CD51, CD166, and CD73 were capable of forming invasive and metastatic tumors reminiscent of intrahepatic cholangiocarcinoma (ICC): they were positive for CK19 and CK7, featured associations of cord-like structures, and contained cuboidal and atypical cells with dissimilar degrees of pleomorphism and mitosis. The LGR5+-derived tumors exhibited a highly vascularized stroma with substantial fibrosis. In addition, we identified pro-angiogenic factors and signaling pathways involved in neo-angiogenesis and vascular development, which represent potential new targets for anti-angiogenic strategies to overcome tumor resistance to current ICC treatments., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2024
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36. [Pancreatoblastoma: A rare entity to be known].

Author: Khneisser P and Bani MA
Subjects: Humans, Pancreatic Neoplasms diagnosis
Published: 2022
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37. Erratum to "Sarcome avec transcrit de fusion EWSR1-PATZ1 Une nouvelle observation avec revue de la littérature" [Ann. Pathol. 41 (2021) 207-211/1513].

Author: Ngo C, Khneisser P, Kanaan C, Valent A, Dumont S, Adam J, and Scoazec JY
Published: 2022
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38. NF1 -Associated Inflammatory Polyp of the Colon: First Report of a Sporadic Case.

Author: Kanaan C, Cotteret S, Khneisser P, Soufan R, Bani MA, Burtin P, Sourrouille I, Ducreux M, Al Ghuzlan A, and Scoazec JY
Subjects: Cecum pathology, Colon pathology, Female, Humans, Inflammation pathology, Middle Aged, Exome Sequencing, Neurofibromatosis 1 complications, Neurofibromatosis 1 diagnosis, Neurofibromatosis 1 genetics, Polyps complications, Polyps diagnosis, Polyps genetics
Abstract: "Juvenile-like (hyperplastic/inflammatory) mucosal polyp" is a term proposed for rare benign mesenchymal lesions of the gastro-intestinal tract so far reported only in patients with type 1 neurofibromatosis (NF1). We report here a first sporadic case of NF1 -associated mucosal inflammatory polyp of the colon. The diagnosis was made in a 53-year old female patient with a large polypoid tumor of the cecum. The lesion was predominantly mucosal, made of fibroblast-like cells associated with inflammatory infiltrates rich in eosinophils and containing entrapped, distorted epithelial glands, responsible for the juvenile-like appearance. Whole exome sequencing showed a pathogenic variant of NF1 . The patient had no evidence of NF1; no NF1 mutation was detected in normal tissues. Our observation may support the existence of juvenile-like inflammatory polyps associated with NF1 alterations, either germline or somatic. This justifies to test NF1 in difficult-to-classify gastrointestinal mesenchymal tumors.
Published: 2022
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39. [E-cadherin dislocation in invasive mammary lobular carcinoma].

Author: Bani MA and Joyon N
Subjects: Cadherins, Female, Humans, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Carcinoma, Lobular pathology
Published: 2022
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40. [Surgical de-escalation in gynecologic oncology].

Author: Zaccarini F, Sanson C, Maulard A, Scherier S, Pautier P, Leary A, Genestie C, Chargari C, Morice P, and Gouy S
Subjects: Chemoradiotherapy methods, Conservative Treatment methods, Endometrial Neoplasms pathology, Female, Fertility Preservation methods, Humans, Hysterectomy trends, Lymph Node Excision trends, Neoplasm Staging, Ovarian Neoplasms pathology, Pelvis, Sentinel Lymph Node Biopsy trends, Uterine Cervical Neoplasms pathology, Endometrial Neoplasms surgery, Ovarian Neoplasms surgery, Uterine Cervical Neoplasms surgery
Abstract: The evolution of knowledge in gynecologic oncology is leading to surgical de-escalation in several areas, particularly in lymph node staging. Sentinel lymph node biopsy that was initially used in low and intermediate risk endometrial cancer, has now been extended to high-intermediate and high-risk endometrial cancer. Sentinel lymph node biopsy plays also an important role in the nodal staging of early-stage cervical cancer. The radicality of hysterectomies in patients with early cervical cancer is under debate. Similarly, surgical staging with para-aortic lymphadenectomy in locally advanced cervical cancer should be performed only for few cases. Systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancers is not recommended anymore., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
Published: 2021
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41. [Molecular genotyping in refractory thyroid cancers in 2021: When, how and why? A review from the TUTHYREF network].

Author: de la Fouchardière C, Wassermann J, Calcagno F, Bardet S, Al Ghuzlan A, Borget I, Borson Chazot F, Do Cao C, Buffet C, Zerdoud S, Decaussin-Petrucci M, Godbert Y, and Leboulleux S
Subjects: Anaplastic Lymphoma Kinase genetics, Carcinoma, Medullary pathology, Carcinoma, Medullary therapy, Genes, ras, Humans, Immunotherapy, Molecular Targeted Therapy, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins c-ret genetics, Receptor, trkA genetics, Telomerase genetics, Thyroid Carcinoma, Anaplastic pathology, Thyroid Carcinoma, Anaplastic therapy, Thyroid Neoplasms pathology, Thyroid Neoplasms therapy, Carcinoma, Medullary genetics, Genotype, Mutation, Thyroid Carcinoma, Anaplastic genetics, Thyroid Neoplasms genetics
Abstract: Refractory thyroid cancers include radio-iodine-refractory cancers, metastatic or locally advanced unresectable medullary and anaplastic thyroid cancers. Their management has been based for several years on the use of multi-target kinase inhibitors, with anti-angiogenic action, with the exception of anaplastic cancers usually treated with chemo- and radiotherapy. The situation has recently evolved due to the availability of molecular genotyping techniques allowing the discovery of rare but targetable molecular abnormalities. New treatment options have become available, more effective and less toxic than the previously available multi-target kinase inhibitors. The management of refractory thyroid cancers is therefore becoming more complex both at a diagnosis level with the need to know when, how and why to look for these molecular abnormalities but also at a therapeutic level, innovative treatments being hardly accessible. The cost of molecular analyzes and the access to treatments need also to be homogenized because disparities could lead to inequality of care at a national or international level. Finally, the strategy of identifying molecular alterations and treating these rare tumors reinforces the importance of a discussion in a multidisciplinary consultation meeting., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
Published: 2021
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42. Direct Water-Assisted Laser Desorption/Ionization Mass Spectrometry Lipidomic Analysis and Classification of Formalin-Fixed Paraffin-Embedded Sarcoma Tissues without Dewaxing.

Author: Ogrinc N, Caux PD, Robin YM, Bouchaert E, Fatou B, Ziskind M, Focsa C, Bertin D, Tierny D, Takats Z, Salzet M, and Fournier I
Subjects: Animals, Dogs, Formaldehyde chemistry, Humans, Lasers, Paraffin Embedding, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Tissue Fixation methods, Water, Lipidomics, Sarcoma
Abstract: Background: Formalin-fixed paraffin-embedded (FFPE) tissue has been the gold standard for routine pathology for general and cancer postoperative diagnostics. Despite robust histopathology, immunohistochemistry, and molecular methods, accurate diagnosis remains difficult for certain cases. Overall, the entire process can be time consuming, labor intensive, and does not reach over 90% diagnostic sensitivity and specificity. There is a growing need in onco-pathology for adjunct novel rapid, accurate, reliable, diagnostically sensitive, and specific methods for high-throughput biomolecular identification. Lipids have long been considered only as building blocks of cell membranes or signaling molecules, but have recently been introduced as central players in cancer. Due to sample processing, which limits their detection, lipid analysis directly from unprocessed FFPE tissues has never been reported., Methods: We present a proof-of-concept with direct analysis of tissue-lipidomic signatures from FFPE tissues without dewaxing and minimal sample preparation using water-assisted laser desorption ionization mass spectrometry and deep-learning., Results: On a cohort of difficult canine and human sarcoma cases, classification for canine sarcoma subtyping was possible with 99.1% accuracy using "5-fold" and 98.5% using "leave-one-patient out," and 91.2% accuracy for human sarcoma using 5-fold and 73.8% using leave-one-patient out. The developed classification model enabled stratification of blind samples in <5 min and showed >95% probability for discriminating 2 human sarcoma blind samples., Conclusion: It is possible to create a rapid diagnostic platform to screen clinical FFPE tissues with minimal sample preparation for molecular pathology., (© American Association for Clinical Chemistry 2021.)
Published: 2021
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43. Erratum à l’article « Tumeur à cellules fusiformes : infection ou néoplasie ? ».

Author: Brunet A, Plouhinec H, Henn A, Scoazec JY, and Ngo C
Published: 2021
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44. [Spindle cell tumor: Infection or neoplasm?]

Author: Brunet A, Plouhinec H, Henn A, Scoazec JY, and Ngo C
Subjects: Humans, Immunohistochemistry, Liposarcoma
Published: 2021
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45. EWSR1-PATZ1 fusion sarcoma - A new case report and review of the literature

Author: Ngo C, Khneisser P, Kanaan C, Valent A, Dumont S, Adam J, and Scoazec JY
Subjects: Humans, Kruppel-Like Transcription Factors genetics, RNA-Binding Protein EWS genetics, Repressor Proteins genetics, Transcription Factors, Oncogene Proteins, Fusion genetics, Sarcoma, Sarcoma, Ewing diagnosis, Sarcoma, Ewing genetics, Soft Tissue Neoplasms
Abstract: Sarcoma with EWSR1-PATZ1 gene fusion is an exceedingly rare and newly described Ewing-like sarcoma harboring EWSR1 rearrangements involving fusion partners other than ETS family genes. The clinical, histopathologic and immunophenotypic features of cases reported in literature are fairly diverse and not specific. We report a new case report posing real challenges for histological and molecular diagnosis., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
Published: 2021
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46. [Gastric bacterial overgrowth: An unusual histological observation, not to be overlooked].

Author: Langlois V, Joyon N, Farah RB, Chachaty E, and Scoazec JY
Subjects: Aged, Female, Humans, Risk Factors, Gastritis, Proton Pump Inhibitors adverse effects
Abstract: Gastric bacterial overgrowth is a rare situation, which may be associated with short- and long-term complications. It must be known from pathologists, since it might be detected incidentally at histological examination of gastric biopsies. We report here the case of a 74-year old woman, obese, without significant medical history, apart from a gastro-esophageal reflux treated by the long-term administration of proton pump inhibitors (PPI). In this patient, gastric bacterial overgrowth was detected at histological examination of gastric biopsies performed after colectomy for left colon adenocarcinoma. Large clusters of small, round, "coccoid" bacteria were present in the gastric mucus. Their characteristics were suggestive of enterobacteria. Bacterial proliferation was associated with severe and diffuse lesions of active gastritis. The course was rapidly unfavorable, and the patient rapidly deceased with multiple infections and multi-organ failure. In our observation, the pathogenesis of gastric bacterial overgrowth was probably multifactorial. It might have been facilitated by long-term PPI treatment and obesity, which are known risk factors, and promoted, in the post-operative setting, by multiple infections and immune failure. Our observation underlines that gastric bacterial overgrowth might be associated with severe gastritis, which might justify antibiotherapy. Other consequences of prolonged gastric dysbiosis cannot be excluded, such as the promotion of neoplastic lesions., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
Published: 2021
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47. [Epithelial Tumours of the Ovary. Case no 3].

Author: Plouhinec H and Genestie C
Subjects: Adult, Carcinoma, Ovarian Epithelial diagnosis, Female, Histocytochemistry methods, Humans, Immunohistochemistry methods, Neoplasm Grading, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Carcinoma, Ovarian Epithelial pathology
Published: 2020
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48. [Epithelial tumours of the ovary. Case No 4].

Author: Plouhinec H and Genestie C
Subjects: Carcinoma, Ovarian Epithelial diagnosis, Female, Histocytochemistry methods, Humans, Immunohistochemistry methods, Middle Aged, Neoplasm Grading, Neoplasm Metastasis pathology, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Carcinoma, Ovarian Epithelial pathology
Published: 2020
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49. [A nodule of the rectal wall].

Author: Joyon N, Tran S, Sourrouille I, and Scoazec JY
Subjects: Aged, Diagnosis, Differential, Histocytochemistry methods, Humans, Immunohistochemistry methods, Intestinal Mucosa pathology, Male, Rectal Neoplasms diagnosis, Rectal Neoplasms pathology, Choristoma diagnosis, Choristoma pathology, Prostate, Rectum pathology
Published: 2020
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50. Cohort study of occupational cosmic radiation dose and cancer mortality in German aircrew, 1960-2014.

Author: Dreger S, Wollschläger D, Schafft T, Hammer GP, Blettner M, and Zeeb H
Subjects: Aged, Brain Neoplasms etiology, Brain Neoplasms mortality, Cohort Studies, Cosmic Radiation, Dose-Response Relationship, Radiation, Female, Germany epidemiology, Humans, Male, Melanoma etiology, Melanoma mortality, Middle Aged, Radiation Dosage, Neoplasms, Radiation-Induced mortality, Occupational Diseases etiology, Occupational Diseases mortality, Occupational Exposure adverse effects
Abstract: Objectives: To determine cancer mortality compared with the general population and to examine dose-response relationships between cumulative occupational radiation dose and specific cancer outcomes in the German aircrew cohort., Methods: For a cohort of 26 846 aircrew personnel, standardised mortality ratios (SMR) were calculated. Dose-response analyses were carried out using Poisson regression to assess dose-related cancer risks for the period 1960-2014. Exposure assessment comprises recently available dose register data for all cohort members and newly estimated retrospective cabin crew doses for 1960-2003., Results: SMR for all-cause, specific cancer groups and most individual cancers were reduced in all aircrew groups. The only increases were seen for brain cancer in pilots (n=23, SMR 2.01, 95% CI 1.15 to 3.28) and for malignant melanoma (n=10, SMR 1.88, 95% CI 0.78 to 3.85). Breast cancer mortality among female cabin crew was similar to the general population (n=71, SMR 1.06, 95% CI 0.77 to 1.44). Overall median cumulative effective dose was 34.2 mSv (max: 116 mSv) for 1960-2014. No dose-response associations were seen in any of the models. For brain cancer, relative risks were elevated across dose categories. An indicative negative trend with increasing dose category was seen for large intestine cancer in female cabin crew (n=23)., Conclusions: There was no evidence for significant dose-response patterns for the considered cancer types. Interpretation of results remains difficult as cumulative dose is closely related to age. Future work should focus on investigating radiation jointly with other risk factors that may contribute to risks for specific cancers among aircrew., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2020
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