Search

Your search keyword '"Sandrine Eimer"' showing total 24 results
Start Over Author "Sandrine Eimer" Search Limiters Available in Library Collection
24 results on '"Sandrine Eimer"'

1. Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study

Author

Hélène Lasolle, Amandine Ferriere, Alexandre Vasiljevic, Sandrine Eimer, Marie-Laure Nunes, and Antoine Tabarin

Subjects
acromegaly, somatostatin analogs, pegvisomant, cabergoline, Pasireotide-LAR, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Purpose: Little data are available regarding the safety and efficacy of s witching to Pasireotide-LAR monotherapy in acromegaly patients with partial resistance to first-generation somatostatin agonists (1gSRL) who require combination treatment with cabergoline or pegvisomant. Method: In this monocentric prospective study within a tertiary univer sity hospital, 15 consecutive acromegalic adults partially resistant to 1gSRL tre ated with octreotide LAR or lanreotide SR, and cabergoline (n = 4, 3.5 mg/week) or pegvisomant (n = 11, median dose 100 mg/week), were switched to Pasireotide-LAR (8 with 40 mg/mo nth; 7 with 60 mg/month). Immunohistochemical expression level of SSTR5 and the granulation pattern of nine somatotroph adenomas were retrospectively deter mined to test for a correlation with the therapeutic efficacy of Pasireotide-LAR. Results: Median IGF-1 concentration at the first evaluation (median 3 mo nths) was similar to baseline (1.0 vs 1.1 ULN). 11/15 patients had IGF-1 levels ≤1.3 ULN before and after the switch but individual changes were variable. Hype rglycemia was frequent and greater in diabetic patients. 7/15 patients stopped Pasireo tide-LAR due to lack of control of IGF-1 or intolerance. 8/15 patients received Pasireo tide-LAR for a median of 29 months with IGF-1 levels ≤1.3 ULN and acceptable glucose tolerance (median HbA1c 6.1%). Two patients required initiation of oral antidiabetic tr eatment. The intensity of SSTR5 expression and the granulation pattern of adenomas were o f limited value for the prediction of Pasireotide-LAR effectiveness. Conclusion: Pasireotide-LAR may represent a suitable therapeutic alternative in a subset of acromegalic patients requiring combination therapy involving a 1gSRL

Published
2019
Full Text
View/download PDF

2. Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers.

Author

Paolo Puccetti, Francesca Fallarino, Antoine Italiano, Isabelle Soubeyran, Gaetan MacGrogan, Marc Debled, Valerie Velasco, Dominique Bodet, Sandrine Eimer, Marc Veldhoen, Georges C Prendergast, Michael Platten, Alban Bessede, and Gilles J Guillemin

Subjects
Medicine, Science
Abstract

Tumor immune escape mechanisms are being regarded as suitable targets for tumor therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO-1/-2) or tryptophan 2,3-dioxygenase 2 (TDO2), resulting in biostatic tryptophan starvation and l-kynurenine production, which participates in shaping the dynamic relationship of the host's immune system with tumor cells. Current immunotherapy strategies include blockade of IDO-1/-2 or TDO2, to restore efficient antitumor responses. Patients who might benefit from this approach are currently identified based on expression analyses of IDO-1/-2 or TDO2 in tumor tissue and/or enzymatic activity assessed by kynurenine/tryptophan ratios in the serum. We developed a monoclonal antibody targeting l-kynurenine as an in situ biomarker of IDO-1/-2 or TDO2 activity. Using Tissue Micro Array technology and immunostaining, colorectal and breast cancer patients were phenotyped based on l-kynurenine production. In colorectal cancer l-kynurenine was not unequivocally associated with IDO-1 expression, suggesting that the mere expression of tryptophan catabolic enzymes is not sufficiently informative for optimal immunotherapy.

Published
2015
Full Text
View/download PDF

3. Correction: SNP Array Analysis Reveals Novel Genomic Abnormalities Including Copy Neutral Loss of Heterozygosity in Anaplastic Oligodendrogliomas.

Author

Ahmed Idbaih, François Ducray, Caroline Dehais, Célia Courdy, Catherine Carpentier, Simon de Bernard, Emmanuelle Uro-Coste, Karima Mokhtari, Anne Jouvet, Jérôme Honnorat, Olivier Chinot, Carole Ramirez, Patrick Beauchesne, Alexandra Benouaich-Amiel, Joël Godard, Sandrine Eimer, Fabrice Parker, Emmanuelle Lechapt-Zalcman, Philippe Colin, Delphine Loussouarn, Thierry Faillot, Phong Dam-Hieu, Selma Elouadhani-Hamdi, Luc Bauchet, Olivier Langlois, Caroline Le Guerinel, Denys Fontaine, Elodie Vauleon, Philippe Menei, Marie Janette Motsuo Fotso, Christine Desenclos, Pierre Verrelle, François Ghiringhelli, Georges Noel, François Labrousse, Antoine Carpentier, Frédéric Dhermain, Jean-Yves Delattre, and Dominique Figarella-Branger

Subjects
Medicine, Science
Published
2013
Full Text
View/download PDF

4. Inflammatory Myofibroblastic Tumour of the Skull Base

Author

Jean-Philippe Maire, Sandrine Eimer, François San Galli, Valérie Franco-Vidal, Sigolène Galland-Girodet, Aymeri Huchet, and Vincent Darrouzet

Subjects
Otorhinolaryngology, RF1-547
Abstract

Inflammatory myofibroblastic tumors (IMTs) are rare benign clinical and pathological entities. IMTs have been described in the lungs, abdomen, retroperitoneum, and extremities but rarely in the head and neck region. A 38-year-old man presented with headache, right exophthalmia, and right 6th nerve palsy. A CT scan revealed enlargement of the right cavernous sinus and osteolytic lesions of the right sphenoid and clivus. MR imaging showed a large tumor of the skull base which was invading the sella turcica, right cavernous sinus, and sphenoidal sinus. A biopsy was performed and revealed an IMT. Corticosteroids were given for 3 months but were inefficient. In the framework of our pluridisciplinary consultation, fractionated conformal radiotherapy (FRT) was indicated at a low dose; 20 Gy in 10 fractions of 2 Gy over 12 days were delivered. Clinical response was complete 3 months after FRT. Radiological response was subtotal 6 months after FRT. Two years later, the patient is well.

Published
2013
Full Text
View/download PDF

5. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

Author

Ahmed Idbaih, François Ducray, Caroline Dehais, Célia Courdy, Catherine Carpentier, Simon de Bernard, Emmanuelle Uro-Coste, Karima Mokhtari, Anne Jouvet, Jérôme Honnorat, Olivier Chinot, Carole Ramirez, Patrick Beauchesne, Alexandra Benouaich-Amiel, Joël Godard, Sandrine Eimer, Fabrice Parker, Emmanuelle Lechapt-Zalcman, Philippe Colin, Delphine Loussouarn, Thierry Faillot, Phong Dam-Hieu, Selma Elouadhani-Hamdi, Luc Bauchet, Olivier Langlois, Caroline Le Guerinel, Denys Fontaine, Elodie Vauleon, Philippe Menei, Marie Janette Motsuo Fotso, Christine Desenclos, Pierre Verrelle, François Ghiringhelli, Georges Noel, François Labrousse, Antoine Carpentier, Frédéric Dhermain, Jean-Yves Delattre, Dominique Figarella-Branger, and POLA Network

Subjects
Medicine, Science
Abstract

Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.

Published
2012
Full Text
View/download PDF

6. Molecular and clinical diversity in primary central nervous system lymphoma: a LOC Network study

Author

Agusti Alentorn, Isaias Hernández-Verdin, Eva Kirasic, Kirsty Wienand, Sandrine Eimer, Hugues Loiseau, Audrey Rousseau, Jérôme Paillassa, Guido Ahle, Felix Lerintiu, Emmanuelle Uro-Coste, Lucie Oberic, Dominique Figarella-Branger, Olivier Chinot, Guillaume Gauchotte, Luc Taillandier, Jean-Pierre Marolleau, Marc Polivka, Clovis Adam, Renata Ursu, Anna Schimitt, Noemie Barillot, Lucia Nichelli, Fernando Lozano-Sánchez, Maria-José Ibañez-Juliá, Matthieu Peyre, Bertrand Mathon, Yah-se Abada, Frederic Charlotte, Frédéric Davi, Chip Stewart, Aurélien de Reyniès, Sylvain Choquet, Carole Soussain, Caroline Houillier, Bjoern Chapuy, and Khe Hoang-Xuan

Subjects
hemic and lymphatic diseases
Abstract

Primary central nervous system lymphoma (PCNSL) is a distinct extranodal lymphoma presenting with limited stage disease but variable response rates to treatment despite homogenous pathological presentation. The likely underlying molecular heterogeneity and its clinical impact is poorly understood.We performed a comprehensive genome-wide analysis of 147 PCNSL from fresh-frozen tumor tissue from immunocompetent, treatment naïve PCNSL patients, employing whole-exome sequencing, assessment of somatic copy number alterations and DNA methylation, and RNA expression. These data were integrated and correlated with the clinico-radiological characteristics and outcomes of the patients. We validated our results in an independent series of 93 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples.Consensus clustering of multi-omics data identified four robust, non-overlapping, prognostically significant clusters (CS) within PCNSL. The CS1 group, characterized by high proliferation and Polycomb Repressive Complex 2 (PRC2) complex activity had an intermediate outcome between CS2/CS3 and CS4. Patients who had PCNSL with an “immune-hot” (CS4) profile had the most favorable clinical outcome. In contrast, patients with the immune-cold hypermethylated CS2 and the heterogenous-immune CS3 groups had a poor prognosis. Nearly all PCNSL patients with meningeal infiltration harbored HIST1H1E mutations, enriched in the CS3 group. The integrated analysis suggests that the CS4 group may be more susceptible to immunotherapy. The integration of genome-wide data from multi-omics data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that significantly improved the current clinical stratification. This molecular classification using FFPE samples facilitates routine use in clinical practice and provides potential precision-medicine strategies in PCNSL.

Published
2022
Full Text
View/download PDF

7. Machine Learning for Better Prognostic Stratification and Driver Gene Identification Using Somatic Copy Number Variations in Anaplastic Oligodendroglioma

Author

Luc Bauchet, Denys Fontaine, D. Larrieu‐Ciron, M. Andraud, H. Aubriot‐Lorton, Fabien Forest, G. Runavot, Shai Rosenberg, I. Carpiuc, François Labrousse, Christine Desenclos, Annie Laquerrière, Georges Noël, Olivier Chinot, Catherine Godfraind, Patrick Beauchesne, Jean-Yves Delattre, Caroline Dehais, T. Cruel, Danchristian Chiforeanu, F. Dhermain, Dominique Cazals-Hatem, Claude Gaultier, W. Lahiani, Marie-Laure Tanguy, C. Dehais, S. Elouadhani‐Hamdi, Pomone Richard, François Ghiringhelli, Olivier Langlois, Ca. Maurage, Dominique Figarella-Branger, Ahmed Idbaih, Carole Ramirez, Philippe Menei, François Ducray, Benoit Lhermitte, Nabila Elarouci, M. Campone, F. Vandenbos‐Burel, Mj. Motso‐Fotso, C. Blechet, Nicolas Desse, Sandrine Eimer, Valérie Rigau, Agusti Alentorn, Anne Jouvet, Damien Ricard, Mc. Tortel, T. Khallil, Clovis Adam, Hugues Loiseau, L. Bekaert, Henri Sevestre, Chiara Villa, M. Fesneau, Isabelle Quintin-Roue, Antoine Petit, Philippe Colin, Elodie Vauleon, S. Lopez, S. Gaillard, Guillaume Gauchotte, Antoine F. Carpentier, Phong Dam-Hieu, Md. Diebold, Yannick Marie, Thierry Faillot, Serge Milin, Aurélien de Reyniès, Emmanuelle Lechapt-Zalcman, Fabrice Parker, E. Cohen‐Moyal, Delphine Loussouarn, Emmanuelle Uro-Coste, Em. Gueye, Audrey Rousseau, F. Ducray, M‐I Mihai, Aurelie Kamoun, Karima Mokhtari, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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 National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), 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 National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, Cancer Research, DNA Copy Number Variations, Survival, Somatic cell, [SDV]Life Sciences [q-bio], Oligodendroglioma, Machine learning, computer.software_genre, medicine.disease_cause, Cohort Studies, Loss of heterozygosity, 03 medical and health sciences, microRNA, medicine, Humans, Neuro‐Oncology, Copy-number variation, Gene, Pathological, business.industry, Genomics, Glioma, Middle Aged, Prognosis, Precision medicine, 3. Good health, 030104 developmental biology, Oncology, Female, Artificial intelligence, Carcinogenesis, business, computer
Abstract

Background 1p/19q-codeleted anaplastic gliomas have variable clinical behavior. We have recently shown that the common 9p21.3 allelic loss is an independent prognostic factor in this tumor type. The aim of this study is to identify less frequent genomic copy number variations (CNVs) with clinical importance that may shed light on molecular oncogenesis of this tumor type. Materials and Methods A cohort of 197 patients with anaplastic oligodendroglioma was collected as part of the French POLA network. Clinical, pathological, and molecular information was recorded. CNV analysis was performed using single-nucleotide polymorphism arrays. Computational biology and feature selection based on the random forests method were used to identify CNV events associated with overall survival and other clinical-pathological variables. Results Recurrent chromosomal events were identified in chromosomes 4, 9, and 11. Forty-six focal amplification events and 22 focal deletion events were identified. Twenty-four focal CNV areas were associated with survival, and five of them were significantly associated with survival after multivariable analysis. Nine out of 24 CNV events were validated using an external cohort of The Cancer Genome Atlas. Five of the validated events contain a cancer-related gene or microRNA: CDKN2A deletion, SS18L1 amplification, RHOA/MIR191 copy-neutral loss of heterozygosity, FGFR3 amplification, and ARNT amplification. The CNV profile contributes to better survival prediction compared with clinical-based risk assessment. Conclusion Several recurrent CNV events, detected in anaplastic oligodendroglioma, enable better survival prediction. More importantly, they help in identifying potential genes for understanding oncogenesis and for personalized therapy. Implications for Practice Genomic analysis of 197 anaplastic oligodendroglioma tumors reveals recurrent somatic copy number variation areas that may help in understanding oncogenesis and target identification for precision medicine. A machine learning multivariable model built using this genomic information enables better survival prediction.

Published
2018
Full Text
View/download PDF

8. Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study

Author

Amandine Ferriere, Hélène Lasolle, Antoine Tabarin, Marie-Laure Nunes, Alexandre Vasiljevic, and Sandrine Eimer

Subjects
medicine.medical_specialty, Combination therapy, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Pasireotide-LAR, Cabergoline, Internal medicine, Acromegaly, Internal Medicine, medicine, Prospective cohort study, pegvisomant, lcsh:RC648-665, business.industry, Research, medicine.disease, Pasireotide, somatostatin analogs, Somatostatin, chemistry, 030220 oncology & carcinogenesis, Pegvisomant, acromegaly, cabergoline, business, Life study, medicine.drug
Abstract

Purpose Little data are available regarding the safety and efficacy of switching to Pasireotide-LAR monotherapy in acromegaly patients with partial resistance to first-generation somatostatin agonists (1gSRL) who require combination treatment with cabergoline or pegvisomant. Method In this monocentric prospective study within a tertiary university hospital, 15 consecutive acromegalic adults partially resistant to 1gSRL treated with octreotide LAR or lanreotide SR, and cabergoline (n = 4, 3.5 mg/week) or pegvisomant (n = 11, median dose 100 mg/week), were switched to Pasireotide-LAR (8 with 40 mg/month; 7 with 60 mg/month). Immunohistochemical expression level of SSTR5 and the granulation pattern of nine somatotroph adenomas were retrospectively determined to test for a correlation with the therapeutic efficacy of Pasireotide-LAR. Results Median IGF-1 concentration at the first evaluation (median 3 months) was similar to baseline (1.0 vs 1.1 ULN). 11/15 patients had IGF-1 levels ≤1.3 ULN before and after the switch but individual changes were variable. Hyperglycemia was frequent and greater in diabetic patients. 7/15 patients stopped Pasireotide-LAR due to lack of control of IGF-1 or intolerance. 8/15 patients received Pasireotide-LAR for a median of 29 months with IGF-1 levels ≤1.3 ULN and acceptable glucose tolerance (median HbA1c 6.1%). Two patients required initiation of oral antidiabetic treatment. The intensity of SSTR5 expression and the granulation pattern of adenomas were of limited value for the prediction of Pasireotide-LAR effectiveness. Conclusion Pasireotide-LAR may represent a suitable therapeutic alternative in a subset of acromegalic patients requiring combination therapy involving a 1gSRL

Published
2019

9. P04.12 Characteristics of IDH-mutant gliomas with non-canonical IDH mutations

Author

C Ferec, Charlotte Bronnimann, Catherine Carpentier, Caroline Dehais, M. Sanson, A Siegfried, D Cappellen, Dominique Figarella-Branger, J.-Y. Delattre, François Ducray, Jean-Sebastien Frenel, S Lacomme, L Poetsch, Delphine Larrieu-Ciron, Sandrine Eimer, Delphine Loussouarn, and Romuald Seizeur

Subjects
Cancer Research, Mutant, Astrocytoma, Cancer, Biology, medicine.disease, nervous system diseases, Poster Presentations, Oncology, Frontal lobe, Non canonical, Glioma, Mutation (genetic algorithm), Cancer research, medicine, Neurology (clinical), Oligodendroglioma, neoplasms
Abstract

BACKGROUND About 10% of IDH-mutant gliomas harbor non-canonical IDH mutations (non-R132H IDH1 and IDH2 mutations). The aim of the present study was to analyze the characteristics of these gliomas in comparison to those of IDH1 R132H mutant gliomas. MATERIAL AND METHODS We retrospectively analyzed the characteristics of a multicentric series of 161 gliomas with non-canonical IDH mutations and compared them to those of consecutive series of 109 IDH1 R132H mutant gliomas. Medical, radiological and pathological were reviewed. RESULTS Median age at diagnosis was 35 years in gliomas with a non-canonical IDH1 mutation, 42 years in those with an IDH2 mutation and 44 years in those with an IDH1R132H mutation. A familial history of cancer was more frequent in gliomas with a non-canonical IDH mutation than in those with an IDH1 R132H mutation (22,3% vs 5,5%, p CONCLUSION Gliomas with non-canonical IDH mutations are associated with distinct clinical, radiological and histological characteristics. Their prognosis, however, is similar to that of gliomas with canonical IDH mutations.

Published
2019

10. Usefulness of Motor-Evoked Potentials Monitoring for Neurosurgical Treatment of an Unusual Distal Anterior Choroidal Artery Aneurysm

Author

Guillaume Penchet, Charles Champeaux, Vincent Jecko, and Sandrine Eimer

Subjects
medicine.medical_specialty, Ischemia, Case Report, Intra ventricular haemorrhage, Motor evoked potentials, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Anterior choroidal artery, medicine, cardiovascular diseases, Neurosurgical treatment, Cerebral aneurysm, medicine.diagnostic_test, business.industry, General Neuroscience, medicine.disease, Surgery, medicine.anatomical_structure, Ventricle, 030220 oncology & carcinogenesis, Angiography, cardiovascular system, Neurology (clinical), Neurosurgery, Motor evoked potentials monitoring, business, 030217 neurology & neurosurgery, Corticotomy
Abstract

A 35 years old woman presented with an acute meningeal syndrome following an intra ventricular haemorrhage without subarachnoid haemorrhage. The angiography demonstrated a 6 mm partially thrombosed saccular aneurysm at the plexal point of the right anterior choroidal artery (AChoA). It was surgically approached inside the ventricle through a trans-temporal corticotomy. The aneurysm was excised after distal exclusion of the feeding artery under motor-evoked potentials monitoring. Of the 19 cases of distal AChoA aneurysm neurosurgical treatment, this is the only one performed under electrophysiology monitoring, a simple and safe method to detect and prevent motor tract ischemia. We discuss this rare case, along with a comprehensible review of the literature of the previous surgical cases of distal AChoA aneurysms.

Published
2016

11. Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum

Author

Michel Wassef, Marie Karanian, Frédéric Chibon, Isabelle Hostein, Sophie Le Guellec, Tom Lesluyes, Jean-Michel Coindre, Brigitte Le Bail, Isabelle Soubeyran, Gaëlle Pérot, Franck Tirode, Jessica Baud, Sophie Laffont, Lucile Delespaul, François Le Loarer, Claire Castain, Cristina R. Antonescu, Anne-Catherine Baglin, Valérie Costes-Martineau, Sandrine Eimer, Institut Bergonié [Bordeaux], UNICANCER, Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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 (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), Memorial Sloane Kettering Cancer Center [New York], Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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 Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Institut Bergonié - CRLCC Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), CRLCC Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), and TIRODE, Franck

Subjects
0301 basic medicine, Nasal cavity, Male, Pathology, Oncogene Proteins, Fusion, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, S100 protein, Fusion gene, Nuclear Receptor Coactivator 2, 0302 clinical medicine, Paranasal Sinuses, Paired Box Transcription Factors, Prospective Studies, In Situ Hybridization, Fluorescence, Sanger sequencing, Aged, 80 and over, medicine.diagnostic_test, Cell Differentiation, Sarcoma, Middle Aged, musculoskeletal system, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, Phenotype, 030220 oncology & carcinogenesis, embryonic structures, symbols, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Anatomy, Gene Fusion, Nasal Cavity, Paranasal Sinus Neoplasms, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Biology, Article, Pathology and Forensic Medicine, 03 medical and health sciences, symbols.namesake, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, PAX3 Transcription Factor, Aged, MyoD Protein, Retrospective Studies, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, 030104 developmental biology, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Trans-Activators, Surgery, Fluorescence in situ hybridization
Abstract

International audience; Biphenotypic sinonasal sarcoma (BSNS) is a locally aggressive tumor occurring in the sinonasal region. It harbors both myogenic and neural differentiation and is characterized by PAX3 rearrangement with MAML3 as the most frequent fusion partner, but the partner of PAX3 remains unidentified in a subset of cases. About 70 cases have been reported so far. In this study, we report a series of 41 cases with clinical, pathologic, and molecular description. Twenty-five (61%) patients were female individuals, and the median age was 49 years. Tumors arose predominantly in the nasal cavity and ethmoidal sinuses. Local recurrences occurred in 8 cases of the 25 (32%). Histologic features were characteristic of BSNS, with 5 cases showing focal rhabdomyoblastic differentiation. Immunohistochemistry showed a constant positivity of S100 protein and PAX3 and negativity of SOX10. MyoD1 was focally positive in 91% of cases, whereas only 20% were positive for myogenin. Molecular analysis showed a PAX3-MAML3 transcript in 37 cases (90%). RNA sequencing was performed in the 4 negative cases for PAX3-MAML3 fusion, and it showed that 1 case harbored a PAX3-FOXO1 fusion, as previously described in the literature, and 2 novel fusions: PAX3-WWTR1 fusion in 2 cases and PAX3-NCOA2 fusion in 1 case. RNA sequencing results were confirmed by fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and Sanger sequencing. The PAX3-NCOA2-positive case showed focal rhabdomyoblastic differentiation. In conclusion, we report 2 novel fusions (PAX3-WWTR1 and PAX3-NCOA2) in BSNS and show that MyoD1 is more sensitive than myogenin for demonstrating myogenic differentiation in this tumor.

Published
2019
Full Text
View/download PDF

12. Identification of novel recurrent ETV6-IgH fusions in primary central nervous system lymphoma

Author

Dominique Figarella-Branger, Franck Bielle, Clovis Adam, Louis Royer-Perron, Guillaume Gauchotte, David Meyronet, Aurélie Bruno, Chiara Villa, Amithys Rahimian, Blandine Boisselier, Carole Soussain, Fabrice Chrétien, Khê Hoang-Xuan, Caroline Houillier, Sandrine Eimer, Mailys Daniau, Frederic Davi, Karima Mokhtari, Karim Labreche, Justine Guegan, Pierre de la Grange, Agusti Alentorn, Marc Polivka, Audrey Rousseau, Frédéric Lemoine, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), OncoNeuroTek [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], GenoSplice, Ltd, GenoSplice technology, GenoSplice [Paris], iCONICS, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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 National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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 National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomopathologie [Le Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hospices civils de Lyon, hôpital neurologique Pierre-Wertheimer, Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Pathologie [Hôpital Foch], Hôpital Foch [Suresnes], Centre Hospitalier Sainte Anne [Paris], Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Département de Pathologie Cellulaire et Tissulaire [CHU Angers] (Laboratoire d’Histopathologie-Cytopathologie), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital René HUGUENIN (Saint-Cloud), This work is part of the national program Cartes d’Identité des Tumeurs (CIT) funded and developed by the Ligue nationale contre le cancer, the Institut National du Cancer, Association pour la recherche sur les tumeurs cérébrales (ARTC), Cancéropôle Île-de-France 'Emergence 2015-1' (2015-1-EMERG-05-INSERM 6-1), Ligue nationale contre le cancer (Comité du Val d’Oise, R14044DD), Ligue Nationale contre le cancer 'Recherche épidemiologique' (N° PRE2015.LNCC), Fondation pour la Recherche Médicale (FDT20140930968), and the program 'Investissements d’avenir' ANR-10-IAIHU-06, and the Institut National du Cancer (INCa) (Réseau Expert National LOC, Lymphomes Oculo-Cérébraux). This study was supported by the Lymphomes Oculo-Cérébraux (LOC) study group network (Réseau national de centres experts des lymphomes primitifs du système nerveux central), We would like to thank the French LOC Network investigators. Specimens from Marseille were retrieved from the AP-HM tumor bank AC 2013-1786, ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-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 National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Incubateur et Pépinière d'Entreprises Paris-Salpêtrière (iPEPS-ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, Cancer Research, Oncogene Proteins, Fusion, MESH: Central Nervous System Neoplasms, Fusion gene, Central Nervous System Neoplasms, 0302 clinical medicine, hemic and lymphatic diseases, MESH: Middle Aged, medicine.diagnostic_test, Primary central nervous system lymphoma, RNA sequencing, ETV6-IgH, MESH: Follow-Up Studies, Middle Aged, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Survival Rate, Oncology, fusion gene, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Female, Lymphoma, Large B-Cell, Diffuse, MESH: Biomarkers, Tumor, Haploinsufficiency, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Proto-Oncogene Proteins c-ets, MESH: Survival Rate, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Prognosis, 03 medical and health sciences, primary CNS lymphoma, medicine, Biomarkers, Tumor, Humans, Survival rate, MESH: Humans, Proto-Oncogene Proteins c-ets, medicine.disease, MESH: Male, Lymphoma, haploinsufficiency, Repressor Proteins, ETV6, 030104 developmental biology, Cancer research, Immunoglobulin heavy chain, MESH: Lymphoma, Large B-Cell, Diffuse, Neurology (clinical), MESH: Female, Fluorescence in situ hybridization, Follow-Up Studies, MESH: Oncogene Proteins, Fusion
Abstract

International audience; Background: Primary central nervous system lymphoma (PCNSL) represents a particular entity within non-Hodgkin lymphomas and is associated with poor outcome. The present study addresses the potential clinical relevance of chimeric transcripts in PCNSL discovered by using RNA sequencing (RNA-seq).Methods: Seventy-two immunocompetent and newly diagnosed PCNSL cases were included in the present study. Among them, 6 were analyzed by RNA-seq to detect new potential fusion transcripts. We confirmed the results in the remaining 66 PCNSL. The gene fusion was validated by fluorescence in situ hybridization (FISH) using formalin-fixed paraffin-embedded (FFPE) samples. We assessed the biological and clinical impact of one new gene fusion.Results: We identified a novel recurrent gene fusion, E26 transformation-specific translocation variant 6-immunoglobulin heavy chain (ETV6-IgH). Overall, ETV6-IgH was found in 13 out of 72 PCNSL (18%). No fusion conserved an intact functional domain of ETV6, and ETV6 was significantly underexpressed at gene level, suggesting an ETV6 haploinsufficiency mechanism. The presence of the gene fusion was also validated by FISH in FFPE samples. Finally, PCNSL samples harboring ETV6-IgH showed a better prognosis in multivariate analysis, P = 0.03, hazard ratio = 0.33, 95% CI = 0.12-0.88. The overall survival at 5 years was 69% for PCNSL harboring ETV6-IgH versus 29% for samples without this gene fusion.Conclusions: ETV6-IgH is a new potential surrogate marker of PCNSL with favorable prognosis with ETV6 haploinsufficiency as a possible mechanism. The potential clinical impact of ETV6-IgH should be validated in larger prospective studies.

Published
2018
Full Text
View/download PDF

13. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis

Author

Gabriel Viennet, Pascale Varlet, Dominique Figarella-Branger, Anh Tuan Nguyen, Clovis Adam, Dominique Cazals-Hatem, Karima Mokhtari, Henri Sevestre, Fabien Forest, François Labrousse, Catherine Carpentier, Sandrine Eimer, Valérie Rigau, Danchristian Chiforeanu, Marie-Hélène Aubriot-Lorton, Carole Colin, Sophie Michalak, F. Vandenbos, Marie-Claire Tortel, Marie-Pierre Chenard, Annie Laquerrière, Isabelle Quintin-Roue, Pomone Richard, Anne Heitzmann, Delphine Loussouarn, Jean Louis Kemeny, Jean-Yves Delattre, Jean-Michel Vignaud, Caroline Dehais, Anne Jouvet, Emmanuelle Uro-Coste, Chiara Villa, Marie-Danièle Diebold, Pierre-Marie Levillain, Marc Polivka, Emmanuelle Lechapt-Zalcman, and Claude-Alain Maurage

Subjects
Pathology, medicine.medical_specialty, IDH1, Necrosis, Direct sequencing, General Neuroscience, Anaplastic oligodendroglioma, IDH1 R132H, Biology, IDH2, nervous system diseases, Pathology and Forensic Medicine, medicine, Neurology (clinical), Progression-free survival, Anaplastic Oligoastrocytoma, medicine.symptom
Abstract

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

Published
2014
Full Text
View/download PDF

14. Mutational analysis of primary central nervous system lymphoma

Author

Dominique Figarella-Branger, Anne Jouvet, Karim Labreche, Romain Daveau, Catherine Miquel, Sandrine Eimer, Marc Polivka, Blandine Boisselier, Caroline Houillier, Khê Hoang-Xuan, Clovis Adam, Y. Marie, Karima Mokhtari, Aurelie Bruno, and Carole Soussain

Subjects
DNA Mutational Analysis, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Germline, Central Nervous System Neoplasms, INDEL Mutation, hemic and lymphatic diseases, medicine, Humans, Exome, Genetic Predisposition to Disease, B cell differentiation, Exome sequencing, NFΚB, Genetics, B-Lymphocytes, Genetic heterogeneity, Primary central nervous system lymphoma, medicine.disease, Lymphoma, Oncology, Primary CNS lymphoma, Mutation, somatic mutations, Lymphoma, Large B-Cell, Diffuse, Carcinogenesis, exome sequencing, Research Paper
Abstract

Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.

Published
2014
Full Text
View/download PDF

15. Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression

Author

German Reyes-Botero, Caroline Dehais, Ahmed Idbaih, Nadine Martin-Duverneuil, Marion Lahutte, Catherine Carpentier, Eric Letouzé, Olivier Chinot, Hugues Loiseau, Jerome Honnorat, Carole Ramirez, Elisabeth Moyal, Dominique Figarella-Branger, François Ducray, Christine Desenclos, Henri Sevestre, Philippe Menei, Sophie Michalak, Edmond Al Nader, Joel Godard, Gabriel Viennet, Antoine Carpentier, Sandrine Eimer, Phong Dam-Hieu, Isabelle Quintin-Roué, Jean-Sebastien Guillamo, Emmanuelle Lechapt-Zalcman, Jean-Louis Kemeny, Pierre Verrelle, Thierry Faillot, Claude Gaultier, Marie Christine Tortel, Christo Christov, Caroline Le Guerinel, Marie-Hélène Aubriot-Lorton, Francois Ghiringhelli, François Berger, Catherine Lacroix, Fabrice Parker, François Dubois, Claude-Alain Maurage, Edouard-Marcel Gueye, Francois Labrousse, Anne Jouvet, Luc Bauchet, Valérie Rigau, Patrick Beauchesne, Jean-Michel Vignaud, Mario Campone, Delphine Loussouarn, Denys Fontaine, Fanny Vandenbos, Chantal Campello, Pascal Roger, Melanie Fesneau, Anne Heitzmann, Jean-Yves Delattre, Selma Elouadhani, Karima Mokhtari, Marc Polivka, Damien Ricard, Pierre-Marie Levillain, Michel Wager, Philippe Colin, Marie-Danièle Diebold, Dan Chiforeanu, Elodie Vauleon, Olivier Langlois, Annie Laquerriere, Marie Janette Motsuo Fotso, Michel Peoc'h, Marie Andraud, Servane Mouton, Marie-Pierre Chenard, Georges Noel, Nicolas Desse, Raoulin Soulard, Alexandra Amiel-Benouaich, Emmanuelle Uro-Coste, and Frederic Dhermain

Subjects
Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Oligodendroglioma, Gene Expression, Biology, Polymorphism, Single Nucleotide, Genomic Instability, Young Adult, Gene expression, medicine, Humans, Oligodendroglial Tumor, Aged, Neovascularization, Pathologic, medicine.diagnostic_test, Brain Neoplasms, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Isocitrate Dehydrogenase, Gene expression profiling, Isocitrate dehydrogenase, Oncology, Frontal lobe, Chromosomes, Human, Pair 1, Basic and Translational Investigations, Mutation, Female, Neurology (clinical), Chromosome Deletion, Chromosomes, Human, Pair 9, Chromosomes, Human, Pair 19, SNP array
Abstract

BACKGROUND: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.

Published
2013
Full Text
View/download PDF

16. Image-guided, noninvasive, spatiotemporal control of gene expression

Author

Sandrine Eimer, Bruno Quesson, Franck Couillaud, Chrit T. W. Moonen, Roel Deckers, and Josette Arsaut

Subjects
Male, Hyperthermia, Time Factors, Light, Transgene, Genetic enhancement, Bone Marrow Cells, Biology, Mice, In vivo, Gene expression, medicine, Animals, HSP70 Heat-Shock Proteins, Ultrasonics, Whole Body Imaging, Luciferase, Heat shock, Promoter Regions, Genetic, Regulation of gene expression, Multidisciplinary, Muscles, Extremities, Biological Sciences, medicine.disease, Magnetic Resonance Imaging, Molecular biology, Cell biology, Kinetics, Gene Expression Regulation, Luminescent Measurements, Heat-Shock Response, Body Temperature Regulation
Abstract

Spatiotemporal control of transgene expression is of paramount importance in gene therapy. Here, we demonstrate the use of magnetic resonance temperature imaging (MRI)-guided, high-intensity focused ultrasound (HIFU) in combination with a heat-inducible promoter [heat shock protein 70 (HSP70)] for the in vivo spatiotemporal control of transgene activation. Local gene activation induced by moderate hyperthermia in a transgenic mouse expressing luciferase under the control of the HSP70 promoter showed a high similarity between the local temperature distribution in vivo and the region emitting light. Modulation of gene expression is possible by changing temperature, duration, and location of regional heating. Mild heating protocols (2 min at 43°C) causing no tissue damage were sufficient for significant gene activation. The HSP70 promoter was shown to be induced by the local temperature increase and not by the mechanical effects of ultrasound. Therefore, the combination of MRI-guided HIFU heating and transgenes under control of heat-inducible HSP promoter provides a direct, noninvasive, spatial control of gene expression via local hyperthermia.

Published
2009
Full Text
View/download PDF

17. Accumulation of an endogenous tryptophan-derived metabolite in colorectal and breast cancers

Author

Marc Veldhoen, Marc Debled, D. Bodet, Michael Platten, Francesca Fallarino, Isabelle Soubeyran, Georges C. Prendergast, Valérie Velasco, Paolo Puccetti, Alban Bessede, Sandrine Eimer, Antoine Italiano, Gaëtan MacGrogan, and Gilles J. Guillemin

Subjects
medicine.drug_class, Metabolite, medicine.medical_treatment, lcsh:Medicine, Breast Neoplasms, Biology, Monoclonal antibody, chemistry.chemical_compound, Immune system, Antigen, medicine, Humans, lcsh:Science, Multidisciplinary, Catabolism, lcsh:R, Tryptophan, Immunotherapy, chemistry, Immunology, Cancer research, lcsh:Q, Colorectal Neoplasms, Kynurenine, Research Article
Abstract

Tumor immune escape mechanisms are being regarded as suitable targets for tumor therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO-1/-2) or tryptophan 2,3-dioxygenase 2 (TDO2), resulting in biostatic tryptophan starvation and l-kynurenine production, which participates in shaping the dynamic relationship of the host’s immune system with tumor cells. Current immunotherapy strategies include blockade of IDO-1/-2 or TDO2, to restore efficient antitumor responses. Patients who might benefit from this approach are currently identified based on expression analyses of IDO-1/-2 or TDO2 in tumor tissue and/or enzymatic activity assessed by kynurenine/tryptophan ratios in the serum. We developed a monoclonal antibody targeting l-kynurenine as an in situ biomarker of IDO-1/-2 or TDO2 activity. Using Tissue Micro Array technology and immunostaining, colorectal and breast cancer patients were phenotyped based on l-kynurenine production. In colorectal cancer l-kynurenine was not unequivocally associated with IDO-1 expression, suggesting that the mere expression of tryptophan catabolic enzymes is not sufficiently informative for optimal immunotherapy.

Published
2015

18. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

Author

Dominique, Figarella-Branger, Karima, Mokhtari, Caroline, Dehais, Anne, Jouvet, Emmanuelle, Uro-Coste, Carole, Colin, Catherine, Carpentier, Fabien, Forest, Claude-Alain, Maurage, Jean-Michel, Vignaud, Marc, Polivka, Emmanuelle, Lechapt-Zalcman, Sandrine, Eimer, Gabriel, Viennet, Isabelle, Quintin-Roué, Marie-Hélène, Aubriot-Lorton, Marie-Danièle, Diebold, Delphine, Loussouarn, Catherine, Lacroix, Valérie, Rigau, Annie, Laquerrière, Fanny, Vandenbos, Sophie, Michalak, Henri, Sevestre, Michel, Peoch, François, Labrousse, Christo, Christov, Jean-Louis, Kemeny, Marie-Pierre, Chenard, Danchristian, Chiforeanu, François, Ducray, Ahmed, Idbaih, Frederic, Dhermain, Laboratoire d'anatomie pathologique - [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon (HCL), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, U975, Université Paris 06, Service d’Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Anatomie Pathologique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Anatomie Pathologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'anatomie et cytologie pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire d'Anatomie Pathologique [CHU Caen], 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), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie-Neuropathologie, CHU de Bordeaux Pellegrin [Bordeaux], Histologie et Pathologie Moléculaire, Université Bordeaux Segalen - Bordeaux 2, Service Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'anatomie et cytologie pathologiques [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Anatomie Pathologique B, Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et Cytologie Pathologique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), chu de nice, Hôpital Pasteur, Laboratoire Central d’Anatomo Pathologie, Hôpital Pasteur [Nice] (CHU), Département de pathologie cellulaire et tissulaire, CHU d'Angers, 4, rue Larrey, 49100 Angers, France., Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Anatomie et Cytologie Pathologiques, CHU Amiens-Picardie, Service d'Anatomie Pathologique [CHU Limoges], CHU Limoges, Hôpital Henri Mondor, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'anatomie pathologique - Hôpital de Hautepierre Hôpitaux Universitaires de Strasbourg - Université de Strasbourg, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuropathologie Raymond Escourolle [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie 2 [CHU Pitié-Salpêtrière], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d'Anatomie et Cytologie Pathologique [Rouen], AP-HP Hôpital Henri Mondor (Créteil), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Neuropathologie [CHU Pitié Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Nord [CHU - APHM]-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université

Subjects
Cancer Research, Pathology, medicine.medical_specialty, IDH1, Necrosis, Mitotic index, Proliferation index, [SDV]Life Sciences [q-bio], Oligodendroglioma, Biology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Chromosome instability, medicine, Mitotic Index, Humans, Progression-free survival, ComputingMilieux_MISCELLANEOUS, Neovascularization, Pathologic, Brain Neoplasms, Brain, medicine.disease, Isocitrate Dehydrogenase, 3. Good health, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Chromosome abnormality, Neurology (clinical), medicine.symptom, Chromosome Deletion, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery
Abstract

BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AO). METHODS: The histological characteristics of 203 AO patients enrolled in the French national network POLA were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q co-deletion was present in 79% of cases and was associated with alpha-internexin expression (p < 10-4), IDH1/2 mutation (p < 10-4), chromosome 4 loss (p < 10-3), and better overall survival (p < 10-4). Based on mitotic index, microvascular proliferation (MVP) and necrosis, 3 groups of 1p/19q co-deleted AO were identified: AO with more than 5 mitoses per 10-HPF, no MVP and no necrosis, (1), AO with MVP and no necrosis (2) and AO with MVP and necrosis (3). Compared to group 1, group 2 and 3 AO had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared to group 2, group 3 AO had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q co-deleted AO, chromosomal instability was associated with shorter progression free survival (p = 0.024) and shorter overall survival (p = 0.023). CONCLUSIONS: The present study shows that oligodendroglioma with classic histological features remains a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q co-deleted AO are also heterogeneous. Interestingly, mitotic index, MVP and necrosis help to classify them into three groups associated with distinct genomic alterations.

Published
2014
Full Text
View/download PDF

19. Cyclopamine cooperates with EGFR inhibition to deplete stem-like cancer cells in glioblastoma-derived spheroid cultures

Author

Marc-Antoine Belaud-Rotureau, Frédéric Dugay, Sandrine Eimer, Kelly Airiau, Véronique Quillien, Tony Avril, Francis Belloc, Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire d'Hématologie, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Service de Biologie, CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cancer Research, Cyclopamine, [SDV]Life Sciences [q-bio], Blotting, Western, Fluorescent Antibody Technique, Apoptosis, Biology, Erlotinib Hydrochloride, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cancer stem cell, Cell Line, Tumor, Neurosphere, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progenitor cell, In Situ Hybridization, Fluorescence, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, 030304 developmental biology, Comparative Genomic Hybridization, 0303 health sciences, Brain Neoplasms, Veratrum Alkaloids, Cell Differentiation, Drug Synergism, Flow Cytometry, Molecular biology, 3. Good health, ErbB Receptors, Oncology, chemistry, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Cancer cell, Neoplastic Stem Cells, Quinazolines, Neurology (clinical), Erlotinib, Stem cell, Glioblastoma, medicine.drug
Abstract

Putative cancer stem cells have been identified in glioblastoma (GBM), associated with resistance to conventional therapies. Overcoming this resistance is a major challenge to manage this deadly brain tumor. Epidermal growth factor receptor (EGFR) is commonly amplified, over-expressed, and/or mutated in GBM, making it a compelling target for therapy. This study investigates the behavior of 3 primary neurosphere (NS) cell lines and their adherent counterparts originated from human GBM resections, when treated with EGFR–tyrosine kinase inhibitor erlotinib, associated or not with cyclopamine, a hedgehog pathway inhibitor. Adherent cells cultured in the presence of serum expressed the glial fibrillary acidic protein, whereas NS-forming cells cultured in serum-free medium expressed CD133, nestin, and Oct-4, markers of neural stem and progenitor cells. For the 3 adherent cell lines, erlotinib has a moderate effect (50% inhibitory concentration [IC50], >10 µM). Conversely, erlotinib induced a strong cell growth inhibition (IC50

Published
2012
Full Text
View/download PDF

20. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

Author

Emmanuelle Uro-Coste, Luc Bauchet, Jean-Yves Delattre, Caroline Le Guerinel, Phong Dam-Hieu, Christine Desenclos, Alexandra Benouaich-Amiel, Thierry Faillot, Catherine Carpentier, Delphine Loussouarn, Antoine F. Carpentier, Karima Mokhtari, François Labrousse, Georges Noël, Olivier Chinot, Jérôme Honnorat, Simon de Bernard, François Ghiringhelli, Ahmed Idbaih, Pierre Verelle, Selma Elouadhani-Hamdi, Sandrine Eimer, Emmanuelle Lechapt-Zalcman, Dominique Figarella-Branger, Marie Janette Motsuo Fotso, Patrick Beauchesne, Frédéric Dhermain, Joel Godard, Anne Jouvet, Caroline Dehais, Carole Ramirez, Philippe Menei, Célia Courdy, Philippe Colin, Elodie Vauleon, Olivier Langlois, François Ducray, Denys Fontaine, Fabrice Parker, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-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 de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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 de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), AltraBio [Lyon], Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinique de Neurochirurgie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neuro-Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Services de Neurologie [CHU Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service de Neurochirurgie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Service de neurochirurgie [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire d'Anatomie Pathologique [CHU Caen], 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), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurochirurgie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [AP-HP Hôpital Lariboisière], AP-HP Groupe Hospitalier Lariboisière, 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), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), 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), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Neurochirurgie, Centre Hospitalier Universitaire de Nice (CHU Nice), CRLCC Eugène Marquis (CRLCC), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Service de Neurochirurgie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Hôpital Nord (Saint Etienne), Service de Neurochirurgie [CHU Amiens], CHU Amiens-Picardie, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Lipides - Nutrition - Cancer (U866) (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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Paul Strauss, CRLCC Paul Strauss, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Université de Limoges (UNILIM), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Stéroides et système nerveux : physiopathologie moléculaire et clinique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), This work is funded by the French Institut National du Cancer (INCa) and part of the national program Cartes d’Identite´ des Tumeurs H (CIT) (http://cit.liguecancer.net/) funded and developed by the Ligue nationale contre le cancer., Sindou, Philippe, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Neurosciences de Montpellier (INM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Neurochirurgie [CHRU Besançon], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurochirurgie [CHU Angers], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]

Subjects
Male, MESH: Genes, p16, Pathology, Tumor Physiology, Loss of Heterozygosity, Loss of heterozygosity, 0302 clinical medicine, CDKN2A, Gene duplication, Molecular Cell Biology, Basic Cancer Research, MESH: Aged, Multidisciplinary, MESH: Middle Aged, Brain Neoplasms, MESH: Polymorphism, Single Nucleotide, Genomics, Middle Aged, 3. Good health, Neurology, Oncology, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Medicine, Female, Research Article, Adult, medicine.medical_specialty, IDH1, Histology, MESH: Mutation, Science, Oligodendroglioma, Locus (genetics), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, IDH2, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, Genetics, Cancer Genetics, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Oligodendroglioma, Aged, MESH: Loss of Heterozygosity, MESH: Humans, Genes, p16, Chromosome, MESH: Adult, medicine.disease, MESH: Male, MESH: Gene Deletion, Mutation, MESH: Female, 030217 neurology & neurosurgery, Gene Deletion, Neuroscience
Abstract

International audience; Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.

Published
2012
Full Text
View/download PDF

21. Malignant Transformation of a Vestibular Schwannoma Remnant 19 Years after Fractionated Radiation Therapy

Author

Vincent Darrouzet, Clotilde Perret, Valérie Franco-Vidal, Sandrine Eimer, and J.-P. Maire

Subjects
medicine.medical_specialty, Translabyrinthine approach, business.industry, medicine.medical_treatment, Malignant peripheral nerve sheath tumor, Schwannoma, medicine.disease, Cerebellopontine angle, Benign tumor, Malignant transformation, Surgery, Radiation therapy, otorhinolaryngologic diseases, medicine, Atypia, Neurology (clinical), business
Abstract

Purpose: To report a case of malignant transformation of a vestibular schwannoma (VS) 19 years after fractionated radiation therapy (FRT). Method: Case report and literature review. Results: A 45-year-old woman had a gradual loss of hearing in her left ear. CT scan and MRI showed a 4-cm VS in the left cerebellopontine angle. She did not suffer NF2. She underwent a translabyrinthine approach excision in September 1986 and the tumor was partially resected without seventh nerve morbidity. Histological examination of the tumor showed a schwannoma with no sign of atypia. One year later, it was decided to use FRT on the tumor remnant to prevent regrowth. She remained symptom-free, and the tumor remained stable for 18 years. In July 2005, she presented with an acute left facial spasm and an episode of diplopia. MRI revealed a tumor recurrence. After total excision performed in December 2005, histological examination demonstrated a low-grade “malignant peripheral nerve sheath tumor” (MPNST). Immunohistochemical data are reported. Conclusion: This case of malignant transformation of a benign tumor fully complies with Cahan's criteria. This is the eighth case of malignant transformation or second tumor arising after radiation therapy, the seven others being consecutive to gamma knife radiosurgery. The long-term risk of radiation therapy is often underestimated in the literature since not all the cases are reported. Patients should be made aware of the advantages and disadvantages of surgery and radiation therapy in the management of VS, especially NF2 and/or young patients.

Published
2007
Full Text
View/download PDF

22. Abstract 3896: Recurrent TERT promoter mutations in primary central nervous system lymphoma

Author

Khê Hoang-Xuan, Clovis Adam, Amithys Rahimian, Carole Soussain, Catherine Miquel, Karima Mokhtari, Mailys Daniau, Caroline Houillier, Aurélie Bruno, Sandrine Eimer, Dominique Figarella-Branger, Agusti Alentorn, Anne Jouvet, and Marc Polivka

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Telomerase, business.industry, Melanoma, Primary central nervous system lymphoma, Promoter, medicine.disease, Lymphoma, Oncology, Hepatocellular carcinoma, Genotype, Cancer research, medicine, Progression-free survival, business
Abstract

Primary central nervous system lymphoma (PCNSL) is a rare extranodal diffuse large B-cell lymphoma (DLBCL) restricted to the CNS and associated with a poor prognosis. Despite a notable effort contributing to better characterize the genomic basis of these tumors, few molecular abnormalities were proposed as predictive or prognostic biomarkers. Recently, two hotspot mutations, C228T and C250T, and the polymorphism rs2853669, located within TERT core promoter region have known a growing interest due to their prognostic value in a wide range of tumors, including melanoma, hepatocellular carcinoma or glioblastoma. Forty-one PCNSL tumor samples of newly diagnosed PCNSL were sequenced for C228T and C250T TERT somatic mutations. TERT promoter mutations status was correlated with clinical outcome and rs2853669 genotype. We identified C228T and C250T mutations and rs2853669 genotype in 20%, 9.4% and 50%, respectively. No case with co-occurrence of C228T and C250T mutations was identified. C228T mutations, but not C250T, were significantly associated with shorter overall survival (OS) (median OS = 4.5 months vs 33 months for non-mutated, p = 0.0048) and progression free survival (PFS) (median PFS = 3 months vs 11.5 months for non-mutated, p = 0.0260). We found no association between TERT promoter mutations and the rs2853669 genotype. To our knowledge, we showed the presence of TERT promoter mutations in PCNSL for the first time. In addition, C228T promoter mutation was associated with a poor outcome. Considering that these mutations are known to confer enhanced TERT promoter activity, we speculate that an increased telomerase activity could play a role in PCNSL aggressiveness. This work was granted by the LOC study group network (réseau national de centres experts des lymphomes primitifs du SNC, INCa), the Ligue contre le Cancer (Comité du Val d’Oise), the Fondation pour la Recherche Médicale (FDT20140930968), the APHP-CRIC 2013 (assistance publique - hôpitaux de Paris), and the Association pour la Recherche sur les Tumeurs Cérébrales. Citation Format: Aurélie Bruno, Mailys Daniau, Karima Mokhtari, Amithys Rahimian, Marc Polivka, Anne Jouvet, Clovis Adam, Dominique Figarella-Branger, Catherine Miquel, Sandrine Eimer, Caroline Houillier, Carole Soussain, Agusti Alentorn, Khê Hoang-Xuan. Recurrent TERT promoter mutations in primary central nervous system lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3896. doi:10.1158/1538-7445.AM2015-3896

Published
2015
Full Text
View/download PDF

23. Investigation of blood vessels in glioblastoma at a micrometric scale: a comparative study by synchrotron and conventional micro-FTIR

Author

Emmanuelle Barron, Gianfelice Cinque, Katia Wehbe, Isabelle Forfar, Adrian Travo, Gérard Déléris, and Sandrine Eimer

Subjects
Materials science, General Chemical Engineering, Malignant brain tumor, General Engineering, Analytical chemistry, medicine.disease, Synchrotron, Analytical Chemistry, law.invention, Tissue sections, law, Glioma, Globar, medicine, Spectral analysis, Fourier transform infrared spectroscopy, Biomedical engineering, Glioblastoma
Abstract

Glioblastoma, the most malignant brain tumor in humans, is characterized by being severely angiogenic and an increase in vascularization generally worsens the prognosis of patients. Finding the best approach to characterize glioma blood vessels (BVs) is very important in view of helping to determine any specific biomolecular markers of these tumors. In previous work by conventional FTIR spectroscopy we were able to discriminate some molecular markers in order to differentiate between normal and tumor BVs in glioma tissue sections. The aim of the present study was to assess whether FTIR microspectroscopy using a synchrotron radiation (SR) source could provide advantages over a classical globar IR source for detailed spectral analysis on such small features like micro-BVs. Using chemometric analysis such as PCA and HCA, the results show that a high brilliant SR beam provides a very satisfying quality signal compared with the globar source to study spectral images for relevant analysis of glioma big and micro-BVs and determination of subtle molecular markers characterizing them from the surrounding tissue.

Published
2013
Full Text
View/download PDF

24. Discrimination between two different grades of human glioma based on blood vessel infrared spectral imaging

Author

Isabelle Forfar, Katia Wehbe, Sandrine Eimer, Gianfelice Cinque, Boullé, Christelle, DIAMOND Light source, Adaptation cardiovasculaire à l'ischémie, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-EA 2406

Subjects
Human glioma, Pathology, medicine.medical_specialty, Analytical chemistry, Malignancy, Biochemistry, Analytical Chemistry, Blood vessels, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glioma, Spectroscopy, Fourier Transform Infrared, medicine, Animals, Cluster Analysis, Humans, Grading (tumors), Neoplasm Grading, Principal Component Analysis, business.industry, Brain Neoplasms, FPA imaging, medicine.disease, Spectral imaging, Rats, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, FTIR spectroscopy, Grading, medicine.anatomical_structure, Article RECHERCHE, Principal component analysis, Heterografts, Female, business, Blood vessel, Research Paper
Abstract

Gliomas are brain tumours classified into four grades with increasing malignancy from I to IV. The development and the progression of malignant glioma largely depend on the tumour vascularization. Due to their tissue heterogeneity, glioma cases can be difficult to classify into a specific grade using the gold standard of histological observation, hence the need to base classification on a quantitative and reliable analytical method for accurately grading the disease. Previous works focused specifically on vascularization study by Fourier transform infrared (FTIR) spectroscopy, proving this method to be a way forward to detect biochemical changes in the tumour tissue not detectable by visual techniques. In this project, we employed FTIR imaging using a focal plane array (FPA) detector and globar source to analyse large areas of glioma tumour tissue sections via molecular fingerprinting in view of helping to define markers of the tumour grade. Unsupervised multivariate analysis (hierarchical cluster analysis and principal component analysis) of blood vessel spectral data, retrieved from the FPA images, revealed the fine structure of the borderline between two areas identified by a pathologist as grades III and IV. Spectroscopic indicators are found capable of discriminating different areas in the tumour tissue and are proposed as biomolecular markers for potential future use of grading gliomas. Graphical Abstract Infrared imaging of glioma blood vessels provides a means to revise the pathologists’ line of demarcation separating grade III (GIII) from grade IV (GIV) parts. Electronic supplementary material The online version of this article (doi:10.1007/s00216-015-8891-z) contains supplementary material, which is available to authorized users.

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results