Author: "Department of histopathology" - Searchworks@Jio Institute Digital Library Search Results

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11,829 results on '"Department of histopathology"'

1. Histologically Diagnosed Cancers: University of Maiduguri Teaching Hospital Cancer Registry Experience (1994 – 1998)

Author: Ekanem, IA; Department of Histopathology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria, Khalil, MI; Department of Histopathology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria, Hassan, AW; Department of Surgery, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria, Ekanem, IA; Department of Histopathology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria, Khalil, MI; Department of Histopathology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria, and Hassan, AW; Department of Surgery, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
Abstract: The University of Maiduguri Teaching Hospital (UMTH), hospital-based cancer registry was established in 1999. Located in the Department of Histolathology, it is aimed at providing baseline data for medical research, patient management, health planning and cancer prevention. In this report, we have analyzed 880 histologically confirmed cancers seen over a five-year period (January 1994 – December 1998). A slight predominance of cancers in females is observed over the males with a male to female ratio of 1:1.2. Cancers of uterine cervix, followed by skin and breast top the list in females. Skin and bladder cancers are the two commonest malignancies in males. Suggested prevention strategies include health education, cancer screening of high-risk groups and proper control of cancer-associated environmental factors. Mary Slessor Journal of Medicine Vol.3(2) 2003:36-40
Published: 2004

2. Mycobacterium avium Subspecies Paratuberculosis in the Inflamed Gut Tissues of Patients with Crohn???s Disease in China and its Potential Relationship to the Consumption of Cow???s Milk: A Preliminary Study

Author: Department of Surgery, St. George???s Hospital Medical School, London, SW17 ORE, UK; General Surgery, TC-2926D, University of Michigan Health System, 1500 E. Medical Center Dr., Ann Arbor, 48109, MI, USA, Department of Surgery, St. George???s Hospital Medical School, London, SW17 ORE, UK, Department of Histopathology, St. George???s Hospital Medical School, London, SW17 ORE, UK, Department of Surgery, St. George???s Hospital Medical School, London, SW17 ORE, UK; Department of Digestion, Affiliated Hospital to Ningxia Medical University, 78 South Shengli Road, Yinchuan, Ningxia, 750004, China, Ann Arbor, Hermon-Taylor, J., Bull, T.J., Cheng, J., Dalton, P., Cen, S., Finlayson, C., Department of Surgery, St. George???s Hospital Medical School, London, SW17 ORE, UK; General Surgery, TC-2926D, University of Michigan Health System, 1500 E. Medical Center Dr., Ann Arbor, 48109, MI, USA, Department of Surgery, St. George???s Hospital Medical School, London, SW17 ORE, UK, Department of Histopathology, St. George???s Hospital Medical School, London, SW17 ORE, UK, Department of Surgery, St. George???s Hospital Medical School, London, SW17 ORE, UK; Department of Digestion, Affiliated Hospital to Ningxia Medical University, 78 South Shengli Road, Yinchuan, Ningxia, 750004, China, Ann Arbor, Hermon-Taylor, J., Bull, T.J., Cheng, J., Dalton, P., Cen, S., and Finlayson, C.
Abstract: Mycobacterium avium subspecies paratuberculosis infection in domestic livestock is widespread in many countries throughout the world. Studies in Europe and the USA show that M. avium subspecies paratuberculosis can be cultured from retail pasteurized cow???s milk and that these organisms are being transmitted to humans by this route. Most people with chronic inflammation of the intestine of the Crohn???s disease type are infected with these chronic enteric pathogens. The production and consumption of cow???s milk has increased in China and so also has the incidence of Crohn???s disease. The present preliminary investigation was carried out to determine whether M. avium subspecies paratuberculosis is present in the intestinal tissues of Chinese patients with Crohn???s disease who have never left China. Archival paraffin-embedded surgical pathology blocks from patients having surgery for Crohn???s disease (CD) or for cancer (nIBD) in China were studied. M. avium subspecies paratuberculosis was detected by nested IS 900 PCR with Southern blotting and amplicon sequencing. The intestinal tissues of 9 of 13 (69.2%) CD patients and 2 of 14 (14.3%) nIBD patients were IS 900 PCR positive (P??=??0.0063; odds ratio??=??13.5). These initial studies suggest that people in China are exposed to M. avium subspecies paratuberculosis and that as in other countries, the infection is significantly associated with Crohn???s disease. M. avium subspecies paratuberculosis in dairy herds and retail milk in China needs to be investigated.
Published: 2006

3. Pulmonary involvement by Niemann-Pick disease. A report of six cases

Author: David M. Hansell, Andrew G. Nicholson, Sylvie Lantuejoul, R Florio, M Malone, P Hughes, AU Wells, Gilbert Ferretti, R M Bois, C I Mackinlay, A Erichsen, H K Ramadan, Elizabeth Brambilla, Salas, Danielle, Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, Department of radiology, Royal Brompton Hospital, Department of Respiratory Medicine, Department of respiratory medicine, Derriford Hospital, Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Service central de radiologie et d'imagerie médicale, Department of Histopathology, Ullevål University Hospital, and Great Ormond St
Subjects: Adult, Male, MESH: Fatal Outcome, MESH: Pneumonia, medicine.medical_specialty, Pathology, Histology, MESH: Foam Cells, Pulmonary Fibrosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), MESH: Microscopy, Electron, Pathology and Forensic Medicine, Fatal Outcome, [SDV.CAN] Life Sciences [q-bio]/Cancer, Fibrosis, MESH: Niemann-Pick Diseases, medicine, Humans, MESH: Lung, Lung, Niemann-Pick Diseases, MESH: Humans, MESH: Middle Aged, MESH: Pulmonary Fibrosis, business.industry, Respiratory disease, MESH: Adult, Anatomical pathology, General Medicine, Pneumonia, Middle Aged, medicine.disease, MESH: Male, Microscopy, Electron, medicine.anatomical_structure, Lipid pneumonia, Female, Niemann–Pick disease, business, MESH: Female, Foam Cells
Abstract: International audience; AIMS: Although pulmonary involvement is a known cause of morbidity in Niemann-Pick disease, histological features in the lung are not well characterized. The purpose of this study is to document the histological features seen in pulmonary involvement by types B and C Niemann-Pick disease and to correlate them with clinical and imaging data. METHODS AND RESULTS: Surgical lung biopsies from six patients (four with type B and two with type C disease) were reviewed and all showed diffuse endogenous lipid pneumonia, with lesser involvement of the interstitium by fibrosis and foamy macrophage accumulation. In type B disease only, there was also fine cytoplasmic vacuolation within the cytoplasm of ciliated epithelial cells. Neither disease showed foamy changes within pneumocytes. One patient had a bronchial cast removed on whole lung lavage. Electron microscopy showed abnormal lamellar inclusions within lysosomes of affected cells in type B disease. In patients with type C disease, biopsies were undertaken as part of investigations into acute respiratory failure in the context of multiorgan systemic presentation. Three patients with type B disease had clinical disease limited to the lung, all adults (mean age of 40 years) with unexplained diffuse parenchymal lung disease and mainly ground-glass shadowing on high-resolution computed tomography. CONCLUSIONS: Niemann-Pick disease should be considered for any patient with unexplained diffuse endogenous lipid pneumonia, even when disease is limited to the lungs and presentation is during adulthood.
Published: 2006
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4. Correlation of ROS1 immunohistochemistry with ROS1 fusion status determined by fluorescence in situ hybridization

Author: Giulio Rossi, Keith M. Kerr, I. Menzl, Jing Li, D. Smith, Wen Wei Liu, Huan Truong, Richard S.P. Huang, Chitra Manohar, Amy Hanlon Newell, Antonio Marchetti, Jingchuan Li, Jaya Rajamani, Cindy Choi, Patrick Pauwels, Reinhard Buettner, Michael Lee, Erik Thunnissen, Ellen Ordinario, Catherine H. Le, Frédérique Penault-Llorca, Lukas Bubendorf, Greg Pate, Fernando Lopez-Rios, Andrew G. Nicholson, Ivonne Marondel, Aysjm Büge Oz, Amrita Pati, Pathology, Genome British Columbia Proteomics Centre [Victoria] (UVic-Genome BC Proteomics Centre), University of Victoria [Canada] (UVIC), Southwest Jiaotong University (SWJTU), US Department of Energy Joint Genome Institute, U.S Department of Energy, U.S. Department of Energy [Washington] (DOE)-U.S. Department of Energy [Washington] (DOE), Institute of Pathology, University of Bonn Medical Centre, Department of Pathology, Aberdeen University Medical School, Laboratorio de Dianas Terapeuticas, Centro Integral Oncologico Clara Campal, Unit of Molecular Pathology, Clinical Research Center (CRC), CeSI, G. d'Annunzio University Foundation, Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), and VU Medical Center
Subjects: Oncogene Proteins, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, ROS1, medicine, Carcinoma, 030304 developmental biology, 0303 health sciences, Crizotinib, medicine.diagnostic_test, Chemistry, General Medicine, respiratory system, medicine.disease, digestive system diseases, respiratory tract diseases, 3. Good health, Medical Laboratory Technology, 030220 oncology & carcinogenesis, Cancer research, Adenocarcinoma, Immunohistochemistry, Human medicine, medicine.drug, Fluorescence in situ hybridization
Abstract: Context.-The ability to determine ROS1 status has become mandatory for patients with lung adenocarcinoma, as many global authorities have approved crizotinib for patients with ROS1-positive lung adenocarcinoma. Objective.-To present analytical correlation of the VENTANA ROS1 (SP384) Rabbit Monoclonal Primary Antibody (ROS1 [SP384] antibody) with ROS1 fluorescence in situ hybridization (FISH). Design.-The immunohistochemistry (IHC) and FISH analytical comparison was assessed by using 122 non-small cell lung cancer samples that had both FISH (46 positive and 76 negative cases) and IHC staining results available. In addition, reverse transcription-polymerase chain reaction (RT-PCR) as well as DNA and RNA next-generation sequencing (NGS) were used to further examine the ROS1 status in cases that were discrepant between FISH and IHC, based on staining in the cytoplasm of 2+ or above in more than 30% of total tumor cells considered as IHC positive. Here, we define the consensus status as the most frequent result across the 5 different methods (IHC, FISH, RT-PCR, RNA NGS, and DNA NGS) we used to determine ROS1 status in these cases. Results.-Of the IHC scoring methods examined, staining in the cytoplasm of 2+ or above in more than 30% of total tumor cells considered as IHC positive had the highest correlation with a FISH-positive status, reaching a positive percentage agreement of 97.8% and negative percentage agreement of 89.5%. A positive percentage agreement (100%) and negative percentage agreement (92.0%) was reached by comparing ROS1 (SP384) using a cutoff for staining in the cytoplasm of 2+ or above in more than 30% of total tumor cells to the consensus status. Conclusions.-Herein, we present a standardized staining protocol for ROS1 (SP384) and data that support the high correlation between ROS1 status and ROS1 (SP384) antibody. © 2020 College of American Pathologists. All rights reserved. Boehringer Ingelheim; Bristol-Myers Squibb; Pfizer; Novartis; Roche; AbbVie; Merck KGaA Dr Huang, Mr Smith, Dr Menzl, Dr Le, Mr Liu, Dr Ordinario, Dr Manohar, Mr Lee, Mr Rajamani, Mr Truong, Dr Jing Li, Ms Choi, Dr Jingchuan Li, Dr Pati, Dr Hanlon Newell, and Mr Pate are Roche employees and receive a salary from Roche. Dr Bubendorf received research support from Roche and received honoraria related to advisory board meetings (Pfizer, Roche). Dr Buettner is a cofounder and chief scientific officer of Targos Mol. Pathol. Inc, Kassel, Germany. Dr Kerr has received honoraria for advisory work and lectures from Ventana Medical Systems, Roche, and Pfizer; these payments were outside the scope of this work. Dr Lopez-Rios received funding and honoraria from Roche, Pfizer, and Thermo Fischer. Dr Marchetti has received honoraria for advisory work and lectures from Ventana Medical Systems, Roche, and Pfizer; these payments were outside the scope of this work. Dr Marondel is an employee and receives a salary from Pfizer. Dr Nicholson serves as a consultant and receives a fee from Merck, Boehringer Ingelheim, Pfizer (also research grant), Novartis, Astra Zeneca (also payment for lecture), Bristol-Myers Squibb, Roche, and ABBVIE. Dr Pauwels received research grants from Pfizer, Roche, and Astra Zeneca and was paid for attending advisory boards of BMS, MSD Astra Zeneca, Takedo, Roche, and Boehringer. Dr Thunnissen participates in Ventana advisory board meetings. The other authors (Dr Öz, Dr Penault-Llorca, and Dr Rossi) have no relevant financial interest in the products or companies described in this article.
Published: 2020
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5. Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue

Author: Richard Marais, Andrew Furness, Thomas B.K. Watkins, Maise Al-Bakir, Dionysis Papadatos-Pastos, Maryam Razaq, Mairead McKenzie, Lisa Pickering, Peter Ellery, Jonathan Ledermann, Andrew V. Biankin, Richard J. Gilbertson, Peter Cockcroft, Mary Mangwende, Sophie Ward, Mary Falzon, Cristina Naceur-Lombardelli, Carlos Caldas, Karla Pearce, Jacqui Shaw, Salma Kadiri, Lars Dyrskjøt, Mark Linch, Daniel Burgess, Nelson Alexander, Christian H. Ottensmeier, Kevin G. Blyth, Lisa L. Gallegos, Rodelaine Wilson, Hayley Bridger, Fiona H Blackhall, Peter J. Parker, Charles Swanton, Allan Hackshaw, Gert Attard, Gordon Stamp, Dean A. Fennell, Debra H. Josephs, Andrew P. Robinson, Kim Edmonds, Tina Mackay, Mita Afroza Akther, Miriam Mitchison, Sam M. Janes, Giorgia Trevisan, Adrienne M. Flanagan, Alison Cluroe, Henning Walczak, Stuart Horswell, Lena Karapagniotou, Simon Tavaré, Sarah Sarker, Teresa Marafioti, Matt Krebs, Anna Green, Philippe Lamy, Reena Khiroya, Samantha M. Hill, Andrew Tutt, Ashish Chandra, Selvaraju Veeriah, Faye Gishen, Lisa Thompson, Sarah Vaughan, Stacey Stanislaw, Kevin Litchfield, Colin Watts, Caroline Dive, Zayd Tippu, Ron Sinclair, Merche Jimenez-Linan, Lavinia Spain, Lizi Manzano, Zoe Rhodes, Caroline Stirling, Elena Provenzano, Andrew Rowan, Katey S. S. Enfield, Vasiliki Michalarea, Nahid Sheikh, Antonia Toncheva, Charlotte Ferris, James Spicer, Kai-Keen Shiu, Aida Murra, Gerald Langman, Scott Thomas Colville Shepherd, Nicholas McGranahan, Fabio Gomes, Daniel Hochhauser, Hang Xu, Sergio A. Quezada, James Larkin, Siow Ming Lee, Chi-wah Lok, Massimo Loda, Gary Middleton, Hollie Bancroft, Jo Dransfield, David Moore, Jennifer Thomas, Rebecca C. Fitzgerald, Peter Colloby, Annika Fendler, Emma Beddowes, Ultan McDermott, Christopher Abbosh, Uzma Asghar, Martin Forster, John Le Quesne, Katherine F. Leith, Paddy Stone, Bernard Olisemeke, Bruce Tanchel, Laura Farrelly, Grant D. Stewart, Justine Korteweg, Sanjay Jogai, Nnenna Kanu, Desiree Schnidrig, Heidi Rosenbaum, Elaine Borg, Mat Carter, Anthony J. Chalmers, Andrew C. Kidd, Alexandre Harlé, Ula Mahadeva, Crispin T. Hiley, Fiona Byrne, Heather Shaw, Mariam Jamal-Hanjani, Karin A. Oien, Ian Proctor, Joanne Webb, Sioban Fraser, Sarah Howlett, Ruby Stewart, Peter Van Loo, Nadia Yousaf, Tanya Ahmad, Martin Collard, Sanjay Popat, James D. Brenton, Sarah Rudman, Lewis Au, David G. Harrison, Elias Pintus, Patricia Roxburgh, Olivia Curtis, Ben Deakin, Ariana Huebner, Debra Enting, Simranpreet Summan, S. Baijal, Iver Nordentoft, Carol Jones, Haixi Yan, Sebastian Brandner, Tariq Enver, Lara-Rose Iredale, Yvonne Summers, Babu Naidu, Abby Sharp, Stephen Hazell, Aoune Barhoumi, Emma Nye, Robert E. Hynds, Sharmistha Ghosh, Emilia L. Lim, Ben Shum, Nikki Hunter, John Bridgewater, Eleanor Carlyle, Stephan Beck, Nicolai Juul Birkbak, Steve Hazell, Samra Turajlic, Amy Kerr, Ian Tomlinson, Adrian Tookman, Litchfield, Kevin [0000-0002-3725-0914], Birkbak, Nicolai J [0000-0003-1613-9587], Nordentoft, Iver [0000-0003-4856-4086], Dyrskjøt, Lars [0000-0001-7061-9851], Apollo - University of Cambridge Repository, Division of genetics and epidemiology, The institute of cancer research [London], The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Royal Marsden, University of Arizona, University of Western Ontario, Physic and Astronomy Department, University of Western Ontario (UWO), Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Aarhus University Hospital, Cancer Research UK Lung Cancer Centre of Excellence [Londres, Royaume-Uni], University College of London [London] (UCL), Comprehensive Cancer Center, UCL Cancer Institute [University College London], The Wellcome Trust Sanger Institute [Cambridge], Research Department of Pathology, Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Department of histopathology, University College Hospital, Mammalian Genetics Laboratory, Centre for Research on Adaptive Nanostructures and Nanodevices, Trinity College Dublin, Cancer Research UK London Research Institute, Guy's and St Thomas' Hospital [London], Breakthrough Breast Cancer Centre, London Institute of Cancer, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, University of Cambridge [UK] (CAM), Cancer Division [Sydney, Australia] (The Kinghorn Cancer Centre), Garvan Institute of Medical Research [Sydney, Australia], Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, University of Leicester, Experimental Cancer Medicine Centre, University of Southampton-Faculty of Medicine, Moses, Wittemyer, Harrison and Woodruff, P.C., University of Oxford, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), and Garvan Institute of medical research
Subjects: 0301 basic medicine, tumor sequencing, medicine.medical_specialty, Sampling protocol, tumor mutational burden, tumor sampling, Lung Neoplasms, molecular profiling, Biopsy, homogenization, Tissue sample, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, Biomarkers, Tumor, Humans, Solid tumor, lcsh:QH301-705.5, Representative sampling, medicine.diagnostic_test, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Clonal structure, biomarkers, High-Throughput Nucleotide Sequencing, Tumor tissue, tumor hetereogeneity, Tumor Burden, 030104 developmental biology, lcsh:Biology (General), representative sampling, Urinary Bladder Neoplasms, Mutation, Radiology, 030217 neurology & neurosurgery
Abstract: International audience; Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias isinherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mmbiopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB butlow clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure.
Published: 2020
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6. Clinical implications of intratumor heterogeneity : challenges and opportunities

Author: Santiago Ramón y Cajal, Marta Sesé, Salvador J. Diaz-Cano, Javier Hernández-Losa, Claudia Capdevila, Leticia De Mattos-Arruda, Josep Castellví, Trond Aasen, Institut Català de la Salut, [Ramón Y Cajal S] Grup de Patologia molecular translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Barcelona, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sesé M, Aasen T] Grup de Patologia molecular translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Barcelona, Spain. [Capdevila C] Grup de Patologia molecular translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA. [De Mattos-Arruda L] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diaz-Cano SJ] Department of Histopathology, King’s College Hospital and King’s Health Partners, London, UK. [Hernández-Losa J, Castellví J] Grup de Patologia molecular translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Artificial intelligence, Antitumor therapeutics, Tumor cells, Review, Computational biology, Biology, Tumor heterogeneity, Epigenesis, Genetic, fenómenos genéticos::variación genética::heterogeneidad genética [FENÓMENOS Y PROCESOS], neoplasias [ENFERMEDADES], Genetic Heterogeneity, 03 medical and health sciences, 0302 clinical medicine, Intratumor heterogeneity, Neoplasms, Drug Discovery, Tumor Microenvironment, Animals, Humans, Epigenetics, Genetics (clinical), Otros calificadores::/terapia [Otros calificadores], 030304 developmental biology, 0303 health sciences, Tumor microenvironment, Liquid biopsy, Càncer - Tractament, Other subheadings::/therapy [Other subheadings], Therapeutic resistance, Human genetics, Neoplasms [DISEASES], Generacions alternants, Phenotype, 030220 oncology & carcinogenesis, Molecular Medicine, Darwinian selection, Genetic Phenomena::Genetic Variation::Genetic Heterogeneity [PHENOMENA AND PROCESSES]
Abstract: Heterogeneidad intratumoral; Inteligencia artificial; Terapias antitumorales Heterogeneïtat intratumoral; Intel·ligència artificial; Teràpies antitumorals Intratumor heterogeneity; Artificial intelligence; Antitumor therapeutics In this review, we highlight the role of intratumoral heterogeneity, focusing on the clinical and biological ramifications this phenomenon poses. Intratumoral heterogeneity arises through complex genetic, epigenetic, and protein modifications that drive phenotypic selection in response to environmental pressures. Functionally, heterogeneity provides tumors with significant adaptability. This ranges from mutual beneficial cooperation between cells, which nurture features such as growth and metastasis, to the narrow escape and survival of clonal cell populations that have adapted to thrive under specific conditions such as hypoxia or chemotherapy. These dynamic intercellular interplays are guided by a Darwinian selection landscape between clonal tumor cell populations and the tumor microenvironment. Understanding the involved drivers and functional consequences of such tumor heterogeneity is challenging but also promises to provide novel insight needed to confront the problem of therapeutic resistance in tumors. SRYC received support from Fondo de Investigaciones Sanitarias (PI14/01320 and PI17/02247), Redes Temáticas de Investigación Cooperativa en Salud (RD12/0036/0057), CIBERONC (CB16/12/00363), and Generalitat de Catalunya (AGAUR, 2017 SGR 1799 and 2014 SGR 1131). TA received support from Instituto de Salud Carlos III (grants PI16/00772 and CPII16/00042), co-financed by the European Regional Development Fund (ERDF).
Published: 2020

7. Re: Attitudes and opinions regarding asbestos and cancer 1934-1965'

Author: Hourihane, D [Department of Histopathology, Trinity College, Dublin (Ireland)]
Published: 1992
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8. Spatiotemporal immune zonation of the human kidney

Author: Dorin-Mirel Popescu, Steven Lisgo, Nathan Richoz, Grace Collord, Anne Y. Warren, James Nicholson, Sarah J. Farndon, Andrew Filby, Roser Vento-Tormo, Marc Bajénoff, Tevita Aho, Gordon L. Frazer, Kevin W. Loudon, Rachel A. Botting, Matthew D. Young, Joy Ursula Lauren Staniforth, Grant D. Stewart, Martin Del Castillo Velasco-Herrera, Benjamin J. Stewart, Stephen Farrell, Nicholas Coleman, Charlotte Guzzo, James N. Armitage, Menna R. Clatworthy, Emily Stephenson, Johanna Burge, Felipe A. Vieira Braga, Muzlifah Haniffa, Imran Mushtaq, Neil J. Sebire, Thomas J. Mitchell, Kile Green, Susan Lindsay, Lira Mamanova, Krzysztof Polanski, Sam Behjati, Alex Cagan, Alexandra M. Riding, Antony C. P. Riddick, John R. Ferdinand, Dyanne Rampling, Sarah A. Teichmann, Mirjana Efremova, Defence Science and Technology Organisation (DSTO), Australian Government, Great Ormond Street Hospital for Children [London] (GOSH), Newcastle University [Newcastle], Institute of Genetic Medicine, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Histopathology & Pediatric Laboratory Medicine, Great Ormond Street Hospital, Institute of Cellular Medicine [Newcastle], Stewart, Benjamin J [0000-0003-4522-0085], Ferdinand, John R [0000-0003-0936-0128], Young, Matthew D [0000-0003-0937-5290], Mitchell, Thomas J [0000-0003-0761-9503], Loudon, Kevin W [0000-0001-9055-6894], Riding, Alexandra M [0000-0002-6915-5671], Staniforth, Joy UL [0000-0003-2817-0098], Vieira Braga, Felipe A [0000-0003-0206-9258], Botting, Rachel A [0000-0001-9595-4605], Stephenson, Emily [0000-0002-4244-4019], Cagan, Alex [0000-0002-7857-4771], Farndon, Sarah J [0000-0001-6024-4267], Polanski, Krzysztof [0000-0002-2586-9576], Del Castillo Velasco-Herrera, Martin [0000-0001-5956-0211], Guzzo, Charlotte [0000-0003-3742-5961], Collord, Grace [0000-0003-1924-4411], Mamanova, Lira [0000-0003-1463-8622], Aho, Tevita [0000-0001-8456-9285], Mushtaq, Imran [0000-0002-7930-0342], Lisgo, Steven [0000-0001-5186-3971], Lindsay, Susan [0000-0003-2980-4582], Stewart, Grant D [0000-0003-3188-9140], Haniffa, Muzlifah [0000-0002-3927-2084], Teichmann, Sarah A [0000-0002-6294-6366], Behjati, Sam [0000-0002-6600-7665], Clatworthy, Menna R [0000-0002-3340-9828], Apollo - University of Cambridge Repository, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Myeloid, Neutrophils, Transgene, Mice, Transgenic, Biology, Kidney, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Fetus, Single-cell analysis, medicine, Animals, Humans, Myeloid Cells, Lymphocytes, RNA-Seq, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Macrophages, Gene Expression Regulation, Developmental, Epithelial Cells, biochemical phenomena, metabolism, and nutrition, Epithelium, 3. Good health, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, Urinary Tract Infections, bacteria, Female, Single-Cell Analysis, 030217 neurology & neurosurgery, Homeostasis
Abstract: Immune landscape of the human kidney Single-cell RNA sequencing has begun to shed light on the full cellular diversity of specific organs. However, these studies rarely examine organ-specific immune cells. Stewart et al. sequenced healthy adult and fetal kidney samples at a single-cell level to define the heterogeneity in epithelial, myeloid, and lymphoid cells. From this dataset, they identified zonation of cells, with relevance to disease and the varied perturbations that occur in different tumor settings. This profiling of the human kidney generates a comprehensive census of existing cell populations that will help inform the diagnosis and treatment of kidney-related diseases. Science , this issue p. 1461
Published: 2018
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9. New insights in the homotopic and heterotopic connectivity of the frontal portion of the human corpus callosum revealed by microdissection and diffusion tractography

Author: De Benedictis, Alessandro, Petit, Laurent, Descoteaux, Maxime, Marras, Carlo Efisio, Barbareschi, Mattia, Corsini, Francesco, Dallabona, Monica, Chioffi, Franco, Sarubbo, Silvio, Department of Neuroscience and Neurorehabilitation, Neurosurgery Unit, Bambino Ges  u Children’s Hospital – IRCCS, 4 Piazza Sant’Onofrio, Roma, 00165, Italy, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Sherbrooke Connectivity Imaging Lab [Sherbrooke] (SCIL), Département d'informatique [Sherbrooke] (UdeS), Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS)-Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Department of Histopathology, 'S. Chiara' Hospital, Trento APSS – 9 Largo Medaglie D’Oro, Trento, 38122, Italy, Department of Neurosciences, Division of Neurosurgery, 'S. Chiara' Hospital, Trento APSS – 9 Largo Medaglie D’Oro, Trento, 38122, Italy, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: corpus callosum, human white matter, [SCCO.NEUR]Cognitive science/Neuroscience, tractography, blunt dissection, inter-hemispheric connectivity, behavioral disciplines and activities, human white matter r r
Abstract: International audience; Extensive studies revealed that the human corpus callosum (CC) plays a crucial role in providing large–scale bi-hemispheric integration of sensory, motor and cognitive processing, especially within the frontal lobe. However, the literature lacks of conclusive data regarding the structural macroscopic connectivity of the frontal CC. In this study, a novel microdissection approach was adopted, to expose the frontal fibers of CC from the dorsum to the lateral cortex in eight hemispheres and in one entire brain. Post-mortem results were then combined with data from advanced constrained spherical deconvolution in 130 healthy subjects. We demonstrated as the frontal CC provides dense inter-hemispheric connections. In particular, we found three types of fronto-callosal fibers, having a dorso-ventral organization. First, the dorso-medial CC fibers subserve homotopic connections between the homologous medial cortices of the superior frontal gyrus. Second, the ventro-lateral CC fibers subserve homotopic connections between lateral frontal cortices, including both the middle frontal gyrus and the inferior frontal gyrus, as well as heterotopic connections between the medial and lateral frontal cortices. Third, the ventro-striatal CC fibers connect the medial and lateral frontal cortices with the contralateral putamen and caudate nucleus. We also highlighted an intricate crossing of CC fibers with the main association pathways terminating in the lateral regions of the frontal lobes. This combined approach of ex vivo microdissection and in vivo diffusion tractography allowed demonstrating a previously unappreciated three-dimensional architecture of the anterior frontal CC, thus clarifying the functional role of the CC in mediating the inter-hemispheric connectivity.
Published: 2016
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10. Evaluation of area-based collagen scoring by nonlinear microscopy in chronic hepatitis C-induced liver fibrosis

Author: Christophe Odin, William L. Irving, Indra Neil Guha, David Sevrain, Yann Le Grand, Matthieu Dubreuil, G E Dolman, Abed M. Zaitoun, Laboratoire de Spectrométrie et Optique Laser (LSOL), Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Nottingham Digestive Diseases Centre: NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Nottingham University Hospital, Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, UK (UON), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Nottingham University Hospitals NHS Trust (NUH), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, medicine.medical_specialty, Nonlinear microscopy, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Liver fibrosis, Image processing, Medical optics and biotechnology : optical diagnostics for medicine, Article, Chronic hepatitis, Fibrosis, Microscopy, medicine, OCIS Codes (110.2960) Imaging systems : Image analysis(170.1610) Medical optics and biotechnology : Clinical applications(170.3880) Medical optics and biotechnology : Medical and biological imaging(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine(180.4315) Microscopy : Nonlinear microscopy, Human liver, business.industry, medicine.disease, Atomic and Molecular Physics, and Optics, 3. Good health, Intensity (physics), Medical optics and biotechnology : medical and biological imaging, Medical optics and biotechnology : clinical applications, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Imaging systems : image analysis, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Biotechnology
Abstract: International audience; In this paper we analyze a fibrosis scoring method based on measurement of the fibrillar collagen area from second harmonic generation (SHG) microscopy images of unstained histological slices from human liver biopsies. The study is conducted on a cohort of one hundred chronic hepatitis C patients with intermediate to strong Metavir and Ishak stages of liver fibrosis. We highlight a key parameter of our scoring method to discriminate between high and low fibrosis stages. Moreover, according to the intensity histograms of the SHG images and simple mathematical arguments, we show that our area-based method is equivalent to an intensity-based method, despite saturation of the images. Finally we propose an improvement of our scoring method using very simple image processing tools.
Published: 2015
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11. Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis

Author: Margaret Burke, Mary N. Sheppard, Andrew G. Nicholson, Sylvie Lantuejoul, Bryan Corrin, Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, and Salas, Danielle
Subjects: Male, Pathology, Lung Neoplasms, Infarction, Pulmonary capillary hemangiomatosis, Hemosiderosis, Lymphocytic Infiltrate, MESH: Child, Medicine, Hemangioma, Capillary, Child, Lung, MESH: Aged, MESH: Middle Aged, MESH: Pulmonary Veins, Arteries, Middle Aged, medicine.anatomical_structure, Pulmonary Veins, Child, Preschool, Pulmonary venoocclusive disease, Female, Pulmonary Veno-Occlusive Disease, Anatomy, MESH: Pulmonary Veno-Occlusive Disease, Adult, medicine.medical_specialty, Adolescent, Hypertension, Pulmonary, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, MESH: Lung, MESH: Hemangioma, Capillary, MESH: Arteries, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, MESH: Hypertension, Pulmonary, business.industry, MESH: Child, Preschool, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Pulmonary hypertension, MESH: Male, MESH: Lung Neoplasms, Surgery, business, MESH: Female
Abstract: International audience; Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension, regarded by some as distinct entities. However, their presentations are similar and both are associated with poor prognoses. We therefore reviewed 38 specimens [autopsies (n=15), surgical biopsies (n=15), explants (n=7), and pneumonectomy (1 case)] from 35 patients diagnosed as either PVOD (n=30; av. age 34 y, range 4 to 68 y; 19M:11F) or PCH (n=5, av. age 42 y, ranging from 9 months to 60 years; 3M:2F) to assess their interrelationship. PCH was identified in 24 (73%) cases diagnosed as PVOD, either as perivenular foci or diffuse involvement of the pulmonary parenchyma. Other features seen in PVOD were arterial medial hypertrophy and/or intimal fibrosis (88%), hemosiderosis (79%), venulitis (12%), infarction (9%), interstitial fibrosis (sometimes as localized scars) (48%), and a mild lymphocytic infiltrate (67%). In cases diagnosed as PCH, 4 showed venous and arterial changes of PVOD. Cases with PCH also all showed a mild interstitial lymphocytic infiltrate but there was no venulitis or infarction. Capillary proliferation was particularly well demonstrated by CD34 immunostaining and predominantly involved the alveoli, but was also seen within walls of bronchi and pulmonary vessels. Our data suggest that in the majority of cases PCH represents a secondary angioproliferative process caused by postcapillary obstruction rather than a separate disease. The cause of the venous obliteration was not identified but the occasional identification of phlebitis suggests this plays a role in venous damage in some cases.
Published: 2006
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12. The course and the anatomo-functional relationships of the optic radiation: a combined study with ‘post mortem’ dissections and ‘ in vivo ’ direct electrical mapping

Author: Paola Milani, Marco Farneti, Valeria Tugnoli, Enrico Granieri, Enzo Colarusso, Franco Chioffi, Mattia Barbareschi, Alessandro De Benedictis, Hugues Duffau, Umbero Rozzanigo, Silvio Sarubbo, Beatrice Paradiso, Department of Neurosciences, Division of Neurosurgery, 'S. Chiara' Hospital, Trento APSS – 9 Largo Medaglie D’Oro, Trento, 38122, Italy, Department of Neuroscience and Neurorehabilitation, Neurosurgery Unit, Bambino Ges  u Children’s Hospital – IRCCS, 4 Piazza Sant’Onofrio, Roma, 00165, Italy, Department of Histopathology, 'S. Chiara' Hospital, Trento APSS – 9 Largo Medaglie D’Oro, Trento, 38122, Italy, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Male, Histology, Deep Brain Stimulation, 030218 nuclear medicine & medical imaging, Resection, White matter, 03 medical and health sciences, 0302 clinical medicine, Connectome, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Medicine, Trigone of urinary bladder, Visual Pathways, Molecular Biology, Ecology, Evolution, Behavior and Systematics, connectomic surgery, Brain Neoplasms, business.industry, Dissection, Histological Techniques, awake mapping, Glioma, Original Articles, Cell Biology, Anatomy, Middle Aged, Complete hemianopia, Fascicle, Magnetic Resonance Imaging, anatomo-functional study, Diffusion Tensor Imaging, medicine.anatomical_structure, Italy, optic radiations, Klingler's technique, business, Lateral wall, white matter, 030217 neurology & neurosurgery, Developmental Biology, Optic radiation
Abstract: International audience; Even if different dissection, tractographic and connectivity studies provided pure anatomical evidences about the optic radiations (ORs), descriptions of both the anatomical structure and the anatomo-functional relationships of the ORs with the adjacent bundles were not reported. We propose a detailed anatomical and functional study with 'post mortem' dissections and 'in vivo' direct electrical stimulation (DES) of the OR, demonstrating also the relationships with the adjacent eloquent bundles in a neurosurgical 'connectomic' perspective. Six human hemispheres (three left, three right) were dissected after a modified Klingler's preparation. The anatomy of the white matter was analysed according to systematic and topographical surgical perspectives. The anatomical results were correlated to the functional responses collected during three resections of tumours guided by cortico-subcortical DES during awake procedures. We identified two groups of fibres forming the OR. The superior component runs along the lateral wall of the occipital horn, the trigone and the supero-medial wall of the temporal horn. The inferior component covers inferiorly the occipital horn and the trigone, the lateral wall of the temporal horn and arches antero-medially to form the Meyer's Loop. The inferior fronto-occipital fascicle (IFOF) covers completely the superior OR along its entire course, as confirmed by the subcortical DES. The inferior longitudinal fascicle runs in a postero-anterior and inferior direction, covering the superior OR posteriorly and the inferior OR anteriorly. The IFOF identification allows the preservation of the superior OR in the anterior temporal resection, avoiding post-operative complete hemianopia. The identification of the superior OR during the posterior temporal, inferior parietal and occipital resections leads to the preservation of the IFOF and of the eloquent functions it subserves. The accurate knowledge of the OR course and the relationships with the adjacent bundles is crucial to optimize quality of resection and functional outcome.
Published: 2015
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13. Metastases from bronchioloalveolar carcinomas associated with long-standing type 1 congenital cystic adenomatoid malformations. A report of two cases

Author: Elisabeth Brambilla, David M. Hansell, Andrew G. Nicholson, Peter Goldstraw, Sylvie Lantuejoul, Gilbert Ferretti, Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, Department of Surgery, Royal Brompton Hospital, Department of Imaging Royal Brompton Hospital, Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, and Salas, Danielle
Subjects: Pathology, medicine.medical_specialty, MESH: Humans, MESH: Middle Aged, Histology, business.industry, MESH: Adenocarcinoma, MESH: Cystic Adenomatoid Malformation of Lung, Congenital, MESH: Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, MESH: Adenocarcinoma, Bronchiolo-Alveolar, MESH: Male, MESH: Lung Neoplasms, Pathology and Forensic Medicine, Text mining, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2006
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14. Assessment of Aurora A kinase expression in breast cancer: a tool for early diagnosis?

Author: Imen Ferchichi, Samia Sassi Hannachi, Amal Baccar, Raja Marrakchi Triki, Jean Yves Cremet, Khaled Ben Romdhane, Claude Prigent, Amel Ben Ammar El Gaaied, Prigent, Claude, Laboratory of Genetics, Immunology and Human Pathology, Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM)-Université de Tunis El Manar (UTM), Department of Histopathology, The Oncology Institute of Saleh Azaïez, Institut de Génétique et Développement de Rennes (IGDR), 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 ), Tunisian State Secretariat for Research and Technology., 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Cytoplasm, Clinical Biochemistry, 0302 clinical medicine, MESH: Aged, 80 and over, Antibody Specificity, Aurora Kinases, MESH: Early Diagnosis, Aurora A, Aged, 80 and over, MESH: Aged, lcsh:R5-920, 0303 health sciences, MESH: Middle Aged, Carcinoma, Ductal, Breast, General Medicine, Middle Aged, MESH: Young Adult, 030220 oncology & carcinogenesis, immunohistochemistry, Female, lcsh:Medicine (General), Receptors, Progesterone, Adult, MESH: Receptors, Progesterone, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Protein Serine-Threonine Kinases, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, Young Adult, MESH: Aurora Kinases, breast cancer, Genetics, Biomarkers, Tumor, Humans, MESH: Antibody Specificity, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Aged, MESH: Humans, MESH: Carcinoma, Intraductal, Noninfiltrating, MESH: Cytoplasm, Biochemistry (medical), MESH: Adult, MESH: Immunohistochemistry, MESH: Carcinoma, Ductal, Breast, Carcinoma, Intraductal, Noninfiltrating, Early Diagnosis, MESH: Tumor Markers, Biological, Other, MESH: Female, MESH: Breast Neoplasms
Abstract: International audience; Aurora A kinase is overexpressed in many cancers but the status of this protein in the breast cancer often varies. We investigate the expression and localization of Aurora A protein in relation with tumor emergence and progression in breast cancer. Aurora A kinase status was evaluated in 107 patients using immunohistochemistry. The experimental findings showed that high expression of the Aurora A protein was correlated with elevated nuclear grade, low expression of progesterone receptor and positive nodal status. The experimental results showed also that the localization of this kinase shifts from cytoplasm in non malignant adjacent tissue to both cytoplasmic and nuclear compartments in tumoral tissue, suggesting an oncogenic role of the nuclear accumulation. We have, furthermore, detected the overexpression of this protein in non malignant adjacent tissue. The expression of the Aurora A kinase in non malignant tissue may represent an earlier diagnosis tool for breast cancer.
Published: 2013
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15. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.: Molecular Signature of Hepatosplenic T-cell Lymphoma

Author: Travert, Marion, Huang, Yenlin, De Leval, Laurence, Martin-Garcia, Nadine, Delfau-Larue, Marie-Helene, Berger, Françoise, Bosq, Jacques, Brière, Josette, Soulier, Jean, Macintyre, Elizabeth, Marafioti, Teresa, De Reyniès, Aurélien, Gaulard, Philippe, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Anatomic Pathology, Chang Gung Memorial Hospital [Taipei] (CGMH), Service de Pathologie Clinique, Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Service d'immunologie biologique, Centre de Biologie et de Pathologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Department of histopathology, University College Hospital, (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), This work is part of the Carte d'Identité des Tumeurs (CIT) program (http://cit.liguecancer.net/index.php/en) from the Ligue Nationale Contre le Cancer and of the Tenomic project inserm-00730464, version 1 - 10 Sep 2012 supported by a Programme Hospitalier de Recherche Clinique and the Institut National du Cancer (INCa). This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut National du Cancer (INCa), the Plan cancer of the Belgian government, and the Association pour la Recherche Thérapeutique, Génétique et Immunologique dans les Lymphomes (ARTGIL). M.T. was supported by the Fondation pour la Recherche Médicale (DEQ 2010/0318253), Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: MESH: Base Sequence, MESH: Protein-Tyrosine Kinases, MESH: Gene Expression Profiling, MESH: Isochromosomes, MESH: Liver Neoplasms, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: Intracellular Signaling Peptides and Proteins, MESH: Molecular Targeted Therapy, MESH: Chromosome Aberrations, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Genes, Neoplasm, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Molecular Sequence Data, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Adult, MESH: Gene Expression Regulation, Neoplastic, MESH: Cell Lineage, MESH: Splenic Neoplasms, MESH: Cluster Analysis, MESH: Male, MESH: Drug Resistance, Neoplasm, MESH: Crystallins, MESH: Young Adult, MESH: Tumor Markers, Biological, MESH: Lymphoma, T-Cell, MESH: Membrane Proteins, MESH: Female
Abstract: International audience; The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.
Published: 2012
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16. Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells

Author: Amé-Thomas, Patricia, Le Priol, Jérôme, Yssel, Hans, Caron, Gersende, Pangault, Céline, Jean, Rachel, Martin, Nadine, Marafioti, Teresa, Gaulard, Philippe, Lamy, Thierry, Fest, Thierry, Semana, Gilbert, Tarte, Karin, Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of histopathology, University College Hospital, Etablissement Français du Sang Bretagne, EFS, This work was supported by research fundings from the Association pour la recherche sur le cancer (ARC AO 2007), the Institut National du Cancer (INCa translationnel 2010, PLBIO-10-195), and the Association pour le Développement de l'Hémato-Oncologie (ADHO). JLP was supported by a PhD studentship from the Association Leucémie Espoir., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, and Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)
Subjects: MESH: Humans, MESH: Immunophenotyping, MESH: Interleukin-2 Receptor alpha Subunit, MESH: Antigens, CD4, MESH: Flow Cytometry, MESH: Immunohistochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Receptors, CXCR5, follicular helper T cells, MESH: Lymphoma, Follicular, MESH: Gene Expression Profiling, follicular lymphoma, MESH: Cell Survival, follicular regulatory T cells, MESH: B-Lymphocytes, MESH: Reverse Transcriptase Polymerase Chain Reaction, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: T-Lymphocytes, Helper-Inducer
Abstract: International audience; Accumulating evidences indicate that the cellular and molecular microenvironment of follicular lymphoma (FL) has a key role in both lymphomagenesis and patient outcome. Malignant FL B cells are found admixed to specific stromal and immune cell subsets, in particular CD4(pos) T cells displaying phenotypic features of follicular helper T cells (T(FH)). The goal of our study was to functionally characterize intratumoral CD4(pos) T cells. We showed that CXCR5(hi)ICOS(hi)CD4(pos) T cells sorted from FL biopsies comprise at least two separate cell populations with distinct genetic and functional features: (i) CD25(pos) follicular regulatory T cells (T(FR)), and (ii) CD25(neg) T(FH) displaying a FL-B cell supportive activity without regulatory functions. Furthermore, despite their strong similarities with tonsil-derived T(FH), purified FL-derived T(FH) displayed a specific gene expression profile including an overexpression of several genes potentially involved directly or indirectly in lymphomagenesis, in particular TNF, LTA, IL4 or CD40LG. Interestingly, we further demonstrated that these two last signals efficiently rescued malignant B cells from spontaneous and rituximab-induced apoptosis. Altogether, our study demonstrates that tumor-infiltrating CD4(pos) T cells are more heterogeneous than previously presumed, and underlines for the first time the crucial role of T(FH) in the complex set of cellular interactions within FL microenvironment.
Published: 2012
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17. Quantification de la fibrose du foie par microscopie nonlinéaire chez des patients infectes par le virus de l'hépatite C

Author: Sevrain, D., Dolman, G., Zeitoun, A., Irving, W., Guha, I., Odin, Christophe, Le Grand, Yann, Laboratoire de Spectrométrie et Optique Laser (LSOL), Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Nottingham Digestive Diseases Centre: NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Nottingham University Hospital, Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, UK (UON), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Publications Mission ressources et compétences technologiques CNRS, S. Motin, F. Ramaz, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Nottingham University Hospitals NHS Trust (NUH), and Cadieu, Muriel
Subjects: [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.IB]Life Sciences [q-bio]/Bioengineering, ComputingMilieux_MISCELLANEOUS, Multiphoton microscopy, liver fibrosis
Abstract: International audience
Published: 2012

18. Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo

Author: Ben Ahmed, M., Zaraa, I., Rekik, R., Elbeldi-Ferchiou, A., Kourda, N., Belhadj Hmida, N., Abdeladhim, M., Karoui, O., Ben Osman, A., Mokni, M., Louzir, H., Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), Department of Dermatology, Hôpital La Rabta [Tunis], Department of histopathology, and Hôpital Charles Nicolle [Rouen]
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, Adolescent, CD3 Complex, Interleukin-2 Receptor alpha Subunit, Models, Immunological, Vitiligo, Forkhead Transcription Factors, Middle Aged, T-Lymphocytes, Regulatory, Autoimmune Diseases, Young Adult, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Self Tolerance, Disease Progression, Humans, Melanocytes, Female, RNA, Messenger, Cell Division, Aged, T-Lymphocytes, Cytotoxic
Abstract: International audience; Auto-reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitiligo but the mechanism underlying the loss of self-tolerance is unknown. A deregulation of regulatory T-cell biology has recently been suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in seven of 15 cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms, suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was further corroborated by the significant increase of Forkhead box P3 expression in the vitiliginous skin of patients. Our data support the involvement of a functional defect of peripheral regulatory T cells in the pathogenesis of vitiligo and open new possibilities to advance therapeutic approaches.
Published: 2011
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19. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

Author: Rudolf M. Huber, Hisao Asamura, Wilbur A. Franklin, Kim R. Geisinger, M. Tsao, James R. Jett, Bruce E. Johnson, Douglas W. Henderson, Denise R. Aberle, David A Johnson, Rafael Rosell, Ignacio I. Wistuba, Keiko Kuriyama, William D. Travis, Valerie W. Rusch, Victor L. Roggli, Jean-Paul Sculier, Fred R. Hirsch, Paul Van Schil, Douglas B. Flieder, Jin Soo Lee, Keith M. Kerr, Andrew G. Nicholson, Elisabeth Brambilla, Nagahiro Saijo, Yasushi Yatabe, Yuichi Ishikawa, Vincent A. Miller, John H. M. Austin, Christian Brambilla, Masayuki Noguchi, Gregory J. Riely, Iver Petersen, Charles A. Powell, Michael K. Gould, David G. Beer, David Yankelewitz, Masahiro Tsuboi, Kavita Garg, Pan-Chyr Yang, Montserrat Sanchez-Cespedes, Tetsuya Mitsudomi, Philip S. Hasleton, Johan Vansteenkiste, Takashi Takahashi, Erik Thunnissen, Adi F. Gazdar, Giorgio V. Scagliotti, Department of Pathology, Memorial Sloane Kettering Cancer Center [New York], Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Université de Tsukuba = University of Tsukuba, Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, Wake Forest Univ./Medicine Medical Center, Department of Pathology and Molecular Diagnostics, Aichi Cancer Ctr., University of Michigan [Ann Arbor], University of Michigan System, Columbia University [New York], Thoracic Oncology Service, University of Antwerp (UA), Department of Radiology, University of Colorado Anschutz [Aurora], Department of Thoracic Surgery, National Cancer Centre, University of Colorado Cancer Center, University of Colorado [Denver], Department of Thoracic Oncology, Università degli studi di Torino (UNITO)-San Luigi Hospital, Aichi Cancer Center Hospital, Pneumologie, University of Munich, The JFCR Cancer Institute, Oncology and Pulmonary and Critical Care Medicine, Mayo Clinic, Institut d' Investigacions Biomediques Bellvitge (IDIBELL), Programa de Epigenètica y Biología del Cáncer-PEBC, Department of Medicine, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Div. of Molecular Carcinogenesis, Nagoya University, Tokyo Medical University, Department of Pulmonology, University Hospitals Leuven [Leuven], Departments of Pathology and Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], Department of Internal Medicine, National Taiwan University College of Medicine, University of California [Los Angeles] (UCLA), University of California-University of California, INSERM U823, équipe 2 (Bases Moléculaires de la Progression des Cancers du Poumon), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Clinique de pneumologie, CHU Grenoble, Fox Chase Cancer Center, UCHSC at Fitzsimons, The University of Texas Health Science Center at Houston (UTHealth), Pulmonary Medicine, Dept of Histopathology, Central Manchester University Hospital, Flinders Medical Centre, Dana-Farber Cancer Institute [Boston], University of Texas Southwestern Medical Center [Dallas], Aberdeen University Medical School, National Hospital Organization Osaka National Hospital, National Cancer Center Korea, Institute of pathology, Universitätsklinikum Friedrich-Schiller-University (FSU), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany]-Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Medical Center [Durham], Duke University [Durham], Medical Oncology Service, Catalan Institute of Oncology, Medical Oncology Division, Kinki/Kindai University School of Medicine, Kindai University-Kindai University, VU Medical Center, Princess Margaret Hospital, University of Toronto-University of Toronto, Weill Medical College of Cornell University [New York], Pathology, CCA - Oncogenesis, Brambilla, Christian, Università degli studi di Torino = University of Turin (UNITO)-San Luigi Hospital, and University of California (UC)-University of California (UC)
Subjects: Oncology, Lung Neoplasms, Bronchioloalveolar carcinoma, Papillary, Acinar, Mucinous cystadenocarcinoma, medicine.disease_cause, Enteric, Limited resection, 0302 clinical medicine, Micropapillary, Pathology, Computed tomography, Lung, 0303 health sciences, p63, Predictive marker, Pulmonary, Classification, 3. Good health, medicine.anatomical_structure, TTF-1, 030220 oncology & carcinogenesis, Adenocarcinoma, KRAS, Adenocarcinoma in situ, Clear cell, Colloid, EGFR, EML4-ALK, Fetal, Frozen section, Gene amplification, Gene profiling, Histologic, Lepidic, Minimally invasive adenocarcinoma, Molecular, Radiology, Signet ring, Solid, Surgery, Humans, Neoplasm Staging, Societies, Medical, Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Medical, medicine, Atypical adenomatous hyperplasia, Lung cancer, 030304 developmental biology, business.industry, Fetal adenocarcinoma, medicine.disease, Clinical trial, Human medicine, business, Societies
Abstract: Introduction: Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.
Published: 2011
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20. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management

Author: Ganesh, Raghu, Harold R, Collard, Jim J, Egan, Fernando J, Martinez, Juergen, Behr, Kevin K, Brown, Thomas V, Colby, Jean-François, Cordier, Kevin R, Flaherty, Joseph A, Lasky, David A, Lynch, Jay H, Ryu, Jeffrey J, Swigris, Athol U, Wells, Julio, Ancochea, Demosthenes, Bouros, Carlos, Carvalho, Ulrich, Costabel, Masahito, Ebina, David M, Hansell, Takeshi, Johkoh, Dong Soon, Kim, Talmadge E, King, Yasuhiro, Kondoh, Jeffrey, Myers, Nestor L, Müller, Andrew G, Nicholson, Luca, Richeldi, Moisés, Selman, Rosalind F, Dudden, Barbara S, Griss, Shandra L, Protzko, Holger J, Schünemann, University of Washington [Seattle], University of California [San Francisco] (UCSF), University of California, Mater Misericordiae University Hospital, University of Michigan [Ann Arbor], University of Michigan System, Ludwig Maximilians University of Munich, National Jewish Health, Mayo Clinic, Rétrovirus et Pathologie Comparée, Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Tulane University, University of Colorado Cancer Center [Aurora, CO, USA], University of Colorado [Boulder], Royal Brompton Hospital, Imperial College London, Hospital Universitario La Princesa, University Hospital of Alexandroupolis, Partenaires INRAE, Universidade de São Paulo (USP), Tohoku University [Sendai], Royal Brompton and Harefield NHS Foundation Trust, Osaka University [Osaka], University of Ulsan, Department of Respiratory Medicine and Allergy, University of British Columbia (UBC), Department of Histopathology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Instituto Nacional de Enfermedades Respiratorias, Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], and Department of Medicine
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Evidence-based practice, diagnosis, International Cooperation, Medizin, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Japan, Medical, Intensive care, therapeutics, Medicine, Humans, usual interstitial pneumonia, Europe, Evidence-Based Medicine, Humans, Idiopathic Pulmonary Fibrosis, diagnosis/therapy, International Cooperation, Japan, Latin America, Societies, Medical, United States, Intensive care medicine, Societies, Medical, Evidence-Based Medicine, business.industry, Interstitial lung disease, Guideline, Evidence-based medicine, medicine.disease, idiopathic pulmonary fibrosis, Combined pulmonary fibrosis and emphysema, Idiopathic Pulmonary Fibrosis, United States, 3. Good health, Surgery, Natural history, Europe, Latin America, diagnosis/therapy, 030228 respiratory system, 030220 oncology & carcinogenesis, Societies, business, evidence-based medicine
Abstract: International audience; This document is an international evidence-based guideline on the diagnosis and management of idiopathic pulmonary fibrosis, and is a collaborative effort of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. It represents the current state of knowledge regarding idiopathic pulmonary fibrosis (IPF), and contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For the diagnosis and treatment sections, pragmatic GRADE evidence-based methodology was applied in a question-based format. For each diagnosis and treatment question, the committee graded the quality of the evidence available (high, moderate, low, or very low), and made a recommendation (yes or no, strong or weak). Recommendations were based on majority vote. It is emphasized that clinicians must spend adequate time with patients to discuss patients' values and preferences and decide on the appropriate course of action.
Published: 2011
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21. Prognostic utility of β-tubulin isotype III and correlations with other molecular and clinicopathological variables in patients with early breast cancer: A translational Hellenic Cooperative Oncology Group (HeCOG) study

Author: Pentheroudakis, George, Batistatou, Anna, Kalogeras, K. T., Kronenwett, R., Wirtz, R. M., Bournakis, E., Eleftheraki, A. G., Pectasides, Dimitrios, Bobos, M., Papaspirou, I., Kamina, S., Gogas, H., Koutras, A. K., Pavlidis, Nicholas, Fountzilas, George, Pavlidis, Nicholas [0000-0002-2195-9961], Pentheroudakis, George [0000-0002-6632-2462], Department of Medical Oncology, Ioannina University Hospital, Department of Pathology, School of medicine [Thessaloniki], Aristotle University of Thessaloniki-Aristotle University of Thessaloniki, Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Siemens Healthcare Diagnostics, Sividon Diagnostics GmbH, Stratifyer Molecular Pathology GmbH, Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Section of Biostatistics, Section of Oncology, 2nd Department of Internal Medicine, Hippokration Hospital, University of Athens School of Medicine, Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Department of Histopathology, Alexandra Hospital, 1st Department of Medicine, Laiko General Hospital, University of Athens School of Medicine, Division of Oncology, Department of Medicine, and University Hospital, University of Patras Medical School
Subjects: Oncology, Β-tubulin isotype iii, Messenger rna, Progesterone receptor, Multiple cycle treatment, Breast cancer, Medicine, Protein analysis, skin and connective tissue diseases, Disease free survival, β-tubulin isotype III, Mastectomy, Gene expression regulation, Genetic transcription, Prognosis, Immunohistochemistry, Gene expression profiling, Gene Expression Regulation, Neoplastic, Retrospective study, Paclitaxel, Granulocyte colony stimulating factor, Reverse transcription polymerase chain reaction, Beta tubulin, Human, medicine.medical_specialty, Tumor gene, Major clinical study, Article, Cancer grading, Epidermal growth factor receptor 2, Prognostic/predictive factors, Humans, Predictive value of tests, RNA, Messenger, Cyclophosphamide, Survival analysis, Retrospective Studies, Aged, TUBB3, Follow up, medicine.disease, Survival Analysis, Retrospective studies, Tamoxifen, Methotrexate, chemistry, Protein expression, Gene expression, Breast neoplasms, Cancer Research, Unclassified drug, Messenger, Partial mastectomy, Beta tubulin iii, Cancer staging, chemistry.chemical_compound, Tubulin, Estrogen receptor, Overall survival, Middle aged, Priority journal, Middle Aged, Excision repair cross complementing protein 1, Female, Breast disease, Fluorouracil, Cancer tissue, Adult, Predictive value, Histopathology, Breast Neoplasms, Young Adult, Predictive Value of Tests, Internal medicine, Tau protein, Early cancer, Human tissue, Neoplasm Staging, Epirubicin, Neoplastic, Taxane, Beta tubulin iii gene, business.industry, Gene Expression Profiling, Cancer, Translational research, Genetic translation, Adjuvant chemotherapy, Drug efficacy, Outcome assessment, Young adult, Multivariate analysis, Multivariate Analysis, Neoplasm staging, Cancer patient, Rna, business, Axillary lymph node, Controlled study
Abstract: We evaluated the prognostic and predictive utility of β-tubulin isotype III (TUBB3) tumour gene transcription in early breast cancer patients enrolled in a randomised study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied for assessment of TUBB3, ER, PgR, HER2 and MAPT messenger RNA and immunohistochemistry (IHC) for protein expression in 314 patients enrolled in trial HE10/97, evaluating epirubicin-alkylator adjuvant chemotherapy with or without paclitaxel. High TUBB3 mRNA status was associated with advanced T stage, high histological grade, low mRNA and protein levels of ER, PgR and MAPT, and high levels of HER2 (p < 0.001). At a median follow-up of 98 months, multivariate analysis showed high TUBB3 mRNA status to have prognostic significance for DFS (HR = 1.83, 95% CI 1.25-2.68, p = 0.002) and OS (HR = 1.71, 95% CI 1.03-2.83, p = 0.038), along with the number of involved axillary nodes, PgR mRNA status and tumour grade. TUBB3 mRNA levels did not predict benefit from inclusion of paclitaxel in adjuvant chemotherapy (test for interaction p = 0.96 for OS, p = 0.46 for DFS). Transcriptional activity of β-tubulin isotype III in early breast cancer is an adverse prognostic factor, though not a predictive one for taxane efficacy. © 2011 Springer Science+Business Media, LLC. 127 1 179 193
Published: 2011
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22. Breast cancer prognostic classification in the molecular era: the role of histological grade

Author: Rakha, Emad A., Reis-Filho, Jorge S., Baehner, Frederick, Dabbs, David J., Decker, Thomas, Eusebi, Vincenzo, Fox, Stephen B., Ichihara, Shu, Jacquemier, Jocelyne, Lakhani, Sunil R., Palacios, José, Richardson, Andrea L., Schnitt, Stuart J., Schmitt, Fernando C., Tan, Puay-Hoon, Tse, Gary M., Badve, Sunil, Ellis, Ian O., [Rakha,EA, and Ellis,IO] Department of Histopathology, Nottingham University Hospital NHS Trust, Nottingham, UK. [Reis-Filho,JS] The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK. [Baehner,F] Department of Anatomic Pathology, University of California, San Francisco, CA, USA. [Dabbs,DJ] University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Decker,T] Breast-Screening-Pathology, Reference Centre Munster, Gerhard Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany. [Eusebi,V] Sezione Anatomia Istologia e Citologia Patologica 'M. Malpighi', Università-ASL Ospedale Bellaria, Bologna, Italia. [Fox,SF] Pathology Department, Peter MacCallum Cancer Centre, East Melbourne, Victoria , Australia. [Ichihara,S] Department of Pathology, Nagoya Medical Center, Naka-ku, Nagoya Japan. [Jacquemier,J] Unité d'Anatomie et de Cytologie Pathologiques, Institut Paoli-Calmettes, Marseille, France. [Lakhani,SR] Molecular and Cellular Pathology, The University of Queensland, Mayne Medical School, Brisbane, Australia. [Palacios,J] Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocio, Sevilla, Spain. [Richardson,AL] Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. [Schnitt,SJ] Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. [Schmitt,FC] Institute of Molecular Pathology and Immunology (IPATIMUP) and Medical Faculty, University of Porto, Porto, Portugal. [Tan,P-H] Department of Pathology, Singapore General Hospital, Singapore. [Tse,GM] Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Shatin, Hong Kong. [Badve,S] Departments of Pathology and Internal Medicine, Clarian Pathology Lab of Indiana University, Indianapolis, USA.
Subjects: Regulación neoplásica de la expresión génica, Perfilación de la expresión génica, Femenino, Pronóstico, Ganglios linfáticos, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Health Status Indicators::Severity of Illness Index [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Tumor Burden [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Anatomy::Tissues::Lymphoid Tissue::Lymph Nodes [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings]
Abstract: Journal Article; Review; Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers. Yes
Published: 2010

23. The Multiple Roles of the Innate Immune System in the Regulation of Apoptosis and Inflammation in the Brain

Author: Philippe Gasque, James Neal, Mark R. Griffiths, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], and Department of Histopathology, Cardiff University
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], Inflammation, Apoptosis, Biology, Pathology and Forensic Medicine, Apoptotic cell clearance, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Immune system, Phagocytosis, medicine, Animals, Humans, 030304 developmental biology, Neurons, 0303 health sciences, Innate immune system, Microglia, Brain, General Medicine, Immunity, Innate, Cell biology, Cytokine, medicine.anatomical_structure, Neurology, Neuroglia, Tumor necrosis factor alpha, Neurology (clinical), medicine.symptom, 030215 immunology
Abstract: International audience; Central nervous system (CNS) tissues contain cells (i.e. glia and neurons) that have innate immune functions. These cells express a range of receptors that are capable of detecting and clearing apoptotic cells and regulating inflammatory responses. Phagocytosis of apoptotic cells is a nonphlogistic (i.e. noninflammatory) process that provides immune regulation through anti-inflammatory cytokines andregulatory T cells. Neurons and glia express cellular death signals, including CD95Fas/CD95L, FasL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor receptor 1 (TNFR), through which they can trigger apoptosis in T cells and other infiltrating cells. Microglia, astrocytes, ependymal cells, and neurons express defense collagens and scavenger and phagocytic receptors that recognize apoptotic cells displaying apoptotic cell-associated molecular patterns, which serve as markers of "altered self." Glia also express pentraxins and complement proteins (C1q, C3b, and iC3b) that opsonize apoptotic cells, making them targets for the phagocytic receptors CR3 and CR4. Immunoregulatory molecules such as the complement regulator CD46 are lost from apoptotic cells and stimulate phagocytosis, whereas the expression of CD47 and CD200 is upregulated during apoptosis; this inhibits proinflammatory microglial cytokine expression, thereby reducing the severity of inflammation. This review outlines the cellular pathways used for the detection and phagocytosis of apoptotic cells in vitro and in experimental models of CNS inflammation.
Published: 2009
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24. Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration

Author: Abdelmadjid Hamri, Paulo Alegria, Mathieu Anheim, Alexander Lossos, Masatoyo Nishizawa, Kiyoshi Iwabuchi, Cyril Goizet, José Leal Loureiro, Christel Depienne, Paula Coutinho, Florence Pasquier, Anne Kjersti Erichsen, Amir Boukhris, Vítor Tedim Cruz, Sylvie Forlani, Chokri Mhiri, Jeremy Truchetto, Filippo M. Santorelli, Alexandra Durr, Paola S. Denora, Christine Tranchant, Isabelle Le Ber, José Vale, Imed Feki, Hamid Azzedine, Giovanni Stevanin, Soreya Belarbi, Israela Lerer, G. Uyanik, Vardiela Meiner, Guillaume Garrigues, Alberto Luis Rosa, Alexis Brice, Chantal M. E. Tallaksen, Meriem Tazir, Masayoshi Tada, Victoria Gonzalez-Martinez, Didier Hannequin, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of neurology, Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Service de Neurologie, Hopital Mustapha, Department of Neurology, Hadassah Hebrew University Medical Center [Jerusalem], Laboratorio de Biologia Cellular y Molecular, Fundacion Allende and Sanatorio Allende, Department of Human Genetics, Hadassah-Hebrew University Medical Centre, Hôpital Benbadis, Serviçio Neurologia, Hospital De Egas Moniz, Departamento de Neurologia, Hospital S. Sebastiao, Niigata University, Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Department of Genetics, University Hospital, Neurology Department, CHU Strasbourg, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Neurological Clinic of Yokohama, Yokohama, Department of Histopathology, Ullevål University Hospital, Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ulleval University Hospital, Département de Neurologie, CHU Strasbourg-Hopital Civil, Service de Neurologie [Strasbourg], Unit of Molecular Medicine, IRCCS, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-05-MRAR-0001,Cav3pathies,Approches physiopathologique et moléculaire de la signalisation calcique dans les caveolinopathies musculaires(2005), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, Genetic Linkage, DNA Mutational Analysis, Neurological disorder, MESH: Base Sequence, Corpus callosum, Gastroenterology, Corpus Callosum, MESH: Magnetic Resonance Imaging, MESH: Genotype, 0302 clinical medicine, MESH: Mental Retardation, MESH: Child, MESH: Motor Neuron Disease, MESH: Proteins, Cognitive decline, Age of Onset, MESH: DNA Mutational Analysis, Child, 0303 health sciences, MESH: Spastic Paraplegia, Hereditary, Cognitive disorder, Brain, Magnetic Resonance Imaging, 3. Good health, Pedigree, medicine.anatomical_structure, Phenotype, Child, Preschool, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Paraplegia, Psychology, Adult, medicine.medical_specialty, MESH: Mutation, Adolescent, Genotype, MESH: Pedigree, MESH: Age of Onset, Molecular Sequence Data, Genes, Recessive, MESH: Phenotype, MESH: Corpus Callosum, Lower motor neuron, 03 medical and health sciences, MESH: Brain, Internal medicine, Intellectual Disability, medicine, Humans, Motor Neuron Disease, MESH: Genes, Recessive, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Spastic Paraplegia, Hereditary, MESH: Child, Preschool, Proteins, MESH: Adult, medicine.disease, MESH: Male, MESH: Cognition Disorders, Mutation, Physical therapy, Neurology (clinical), Age of onset, Cognition Disorders, MESH: Female, MESH: Linkage (Genetics), 030217 neurology & neurosurgery, Executive dysfunction
Abstract: Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly characterized by lower limb spasticity associated, in complicated forms, with additional neurological signs. We have analysed a large series of index patients (n = 76) with this condition, either from families with an autosomal recessive inheritance (n = 43) or isolated patients (n = 33), for mutations in the recently identified SPG11 gene. We found 22 truncating mutations, including the first four splice-site mutations, segregating in seven isolated cases and 13 families. Nineteen mutations were novel. Two recurrent mutations were found in Portuguese and North-African patients indicating founder effects in these populations. The mutation frequency varied according to the phenotype, from 41%, in HSP patients presenting with a thin corpus callosum (TCC) visualized by MRI, to 4.5%, in patients with mental impairment without a TCC. Disease onset occurred during the first to the third decade mainly by problems with gait and/or mental retardation. After a mean disease duration of 14.9 +/- 6.6 years, the phenotype of 38 SPG11 patients was severe with 53% of patients wheelchair bound or bedridden. In addition to mental retardation, 80% of the patients showed cognitive decline with executive dysfunction. Interestingly, the phenotype also frequently included lower motor neuron degeneration (81%) with wasting (53%). Slight ocular cerebellar signs were also noted in patients with long disease durations. In addition to a TCC (95%), brain MRI revealed white matter alterations (69%) and cortical atrophy (81%), which worsened with disease duration. In conclusion, our study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC and cognitive impairment, including in isolated patients, and extends the associated phenotype.
Published: 2008
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25. Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 2007

Author: Britt Skogseid, Andrew G. Nicholson, Dik J. Kwekkeboom, James R. Jett, Piero Ferolla, Peter Goldstraw, Eric Lim, John Crowley, Jamshed Bomanji, Martyn Caplin, Eric Baudin, Valerie W. Rusch, William D. Travis, Elisabeth Brambilla, Hisao Asamura, Brambilla, Christian, Imperial College and the Academic Division of Thoracic Surgery, Royal Brompton Hospital, Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, Department of Pathology, Memorial Sloane Kettering Cancer Center [New York], Department of Medical Oncology and Pulmonary Medicine, Mayo Clinic, Department of Internal Medicine and Endocrine Sciences, Università degli Studi di Perugia = University of Perugia (UNIPG), Department of Nuclear Medicine, University College Hospital, Department of Thoracic Surgery, National Cancer Centre, Department of Medical Sciences, Uppsala University, Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Department of Gastroenterology, Royal Free Hospital [London, UK], Erasmus university, INSERM U823, équipe 2 (Bases Moléculaires de la Progression des Cancers du Poumon), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon-Hôpital Michallon, Cancer Research and Biostatistics, Cancer Center, Università degli Studi di Perugia (UNIPG), and Royal Free Hospital
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, MESH: Neuroendocrine Tumors, education, Prospective data, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neuroendocrine tumors, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Typical carcinoid, 03 medical and health sciences, 0302 clinical medicine, Neuroendocrine tumours, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, Medical physics, Lung cancer, health care economics and organizations, 030304 developmental biology, 0303 health sciences, MESH: Humans, business.industry, Carcinoma, Advanced stage, Large cell neuroendocrine, Atypical carcinoid, medicine.disease, 3. Good health, MESH: Lung Neoplasms, Clinical trial, Oncology, Novel agents, 030220 oncology & carcinogenesis, Tissue bank, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Biostatistics, business
Abstract: International audience; The International Association for the Study of Lung Cancer, (IASLC) International Congress on Advances in Pulmonary Neuroendocrine Tumors was a two-day meeting held at the Royal Brompton Hospital in London, United Kingdom on the thirteenth and forteenth of December 2007. The meeting was led by 14 member international faculty-in the disciplines of pathology, surgery, medicine, oncology, endocrinology, nuclear medicine, diagnostic imaging, and biostatistics. The aims were twofold, as an educational meeting, and to develop the IASLC International Pulmonary Neuroendocrine Tumors Registry. The meeting highlighted the difference in presentation of the tumors, management options for early and advanced stage disease including the use of novel agents and approaches. The need, process, and approach to an International Registry of Pulmonary Neuroendocrine Tumors were emphasized. International collaboration to develop a retrospective registry, prospective data collection, virtual tissue bank, and collaborative clinical trials were universally agreed as the best way to advance our understanding and treatment of these rare tumors.
Published: 2008
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26. Mucinous cells in type 1 pulmonary congenital cystic adenomatoid malformation as mucinous bronchioloalveolar carcinoma precursors

Author: Eva Brabencova, Giuliana Sartori, Claire Danel, Christian Piolat, Elisabeth Brambilla, Giulio Rossi, Andrew G. Nicholson, Sylvie Lantuejoul, Peter Goldstraw, Lantuejoul, Sylvie, Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of histopathology, Royal Brompton Hospital-National Heart and Lung Institute Division of Imperial College School of Medicine, Section of Pathologic Anatomy, Azienda Policlinico, Service de chirurgie pédiatrique, CHU Grenoble, Service d'histopathologie (HEGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Department of Pathology Bratislava, NUT a RCH, Department of Thoracic Surgery, and Royal Brompton Hospital
Subjects: Male, Pathology, MESH: Adenocarcinoma, Mucinous, Loss of Heterozygosity, MESH: Adenocarcinoma, Bronchiolo-Alveolar, Polymerase Chain Reaction, Loss of heterozygosity, 0302 clinical medicine, FHIT, MESH: Child, Mucinous carcinoma, CDX2, Child, 0303 health sciences, MESH: Middle Aged, Anatomical pathology, Middle Aged, MESH: Infant, Adenocarcinoma, Mucinous, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, MESH: Precancerous Conditions, 030220 oncology & carcinogenesis, Child, Preschool, Adenocarcinoma, Female, Anatomy, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Immunophenotyping, Adolescent, MESH: Cystic Adenomatoid Malformation of Lung, Congenital, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Pathology and Forensic Medicine, Immunophenotyping, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cystic Adenomatoid Malformation of Lung, Congenital, medicine, Humans, 030304 developmental biology, MESH: Loss of Heterozygosity, MESH: Adolescent, Lung, MESH: Humans, MESH: Child, Preschool, Infant, MESH: Polymerase Chain Reaction, MESH: Adult, MESH: Immunohistochemistry, Adenocarcinoma, Bronchiolo-Alveolar, medicine.disease, MESH: Male, Mutation, Cancer research, Surgery, MESH: Microsatellite Repeats, MESH: Female, Precancerous Conditions, Microsatellite Repeats
Abstract: International audience; Type 1 congenital cystic adenomatoid malformation (CCAM), the most frequent malformation of the lung, is the only type to present intracystic mucinous cell clusters, which may form beyond the cysts extracystic mucinous proliferation resembling mucinous bronchioloalveolar carcinomas (BACs). As mucinous BACs are increasingly described in the literature in young patients with CCAM, we hypothesized that type 1 CCAM mucinous cells could represent BAC precursors. We reviewed 7 cases of type 1 CCAM including 6 with intracystic mucinous cell clusters, 3 with extracystic mucinous proliferations, and 4 with mucinous BAC or mixed adenocarcinoma with predominant BAC. K-ras mutations at codon 12 were detected in 3/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in 3/4 BAC. Loss of heterozygosity (LOH) at p16(INK4) locus, with microsatellite alterations in 3 cases, was observed in 2/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in all BAC. Two extracystic mucinous proliferations showed LOH at FHIT and Rb loci, respectively. P16(INK4) expression was lost in 2 intracystic mucinous cell clusters, 1 extracystic mucinous proliferation, and 1 BAC. Neither epidermal growth factor receptor mutation on exons 18, 19, and 21 nor P53 accumulation was observed. All lesions expressed MUC5AC, but were negative for MUC2, CDX2, and TTF-1. In conclusion, type 1 CCAM mucinous cells share the same differentiation profile with corresponding mucinous BAC, consistent with a common bronchial origin. Moreover, the high frequency of K-ras mutation and LOH and/or microsatellite alterations at p16(INK4) locus presented by these mucinous cells justifies their consideration as BAC precursors.
Published: 2007
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27. Inflammatory breast cancers in Tunisia and France show similar immunophenotypes

Author: Jocelyne Jacquemier, Azza Ben Hamida, Mansour Ben Abdallah, Luc Xerri, Karima Mrad, Benjamin Esterni, Sana Intidhar Labidi, Khaled Ben Romdhane, Patrice Viens, Farhat Ben Ayed, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Amel Mezlini, Daniel Birnbaum, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Department of Histopathology, The Oncology Institute of Saleh Azaïez, Cancérologie (Inserm U599/IPC), Université de la Méditerranée - Aix-Marseille 2-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biopathologie, Université de la Méditerranée - Aix-Marseille 2, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: Adult, Pathology, medicine.medical_specialty, Tunisia, Receptor, ErbB-2, Estrogen receptor, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Inflammatory breast cancer, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, skin and connective tissue diseases, MUC1, 030304 developmental biology, 0303 health sciences, Tissue microarray, business.industry, Carcinoma, Mucin-1, General Medicine, Middle Aged, medicine.disease, Cadherins, 3. Good health, Micropapillary pattern, Ki-67 Antigen, Receptors, Estrogen, 030220 oncology & carcinogenesis, Immunohistochemistry, Surgery, Female, France, business
Abstract: International audience; Purpose: Inflammatory breast cancers (IBC) have specific immunophenotypic profiles as compared to non-inflammatory (non-IBC): combined differential expression of estrogen receptor, Ki67, E-cadherin, MUC1, and ERBB2 can be used as an IBC signature. It is thought that IBC occurs with a high frequency in Tunisia. The aim of this study is to evaluate this signature on a Tunisian series. Methods: The expression of five proteins (E-cadherin, ERBB2, estrogen receptor, Ki67, MUC1) was studied by immunohistochemistry on a consecutive series of 91 cases of IBC (T4D) treated at Tunisian Salah Azaiz Institute (ISA) and deposited in a tissue microarray (TMA). Results were compared to the same study on a series of 85 cases treated in France. Results: The ISA cases were characterized by a significantly younger age of patients (median: 42 years old in ISA for 53.5 in IPC, p = 0.00042) and a higher frequency of invasive micropapillary pattern. None of the five parameters was expressed differentially in the two series. In non-metastatic patients, high level of proliferation (Ki67) and overexpression of ERBB2 were associated with poor outcome. Conclusion: The IBC from Tunisia were not different from those observed in France on the basis of IHC profiles. However, the younger age of the patients suggest a specific epidemiological context that should be investigated. (C) 2007 Elsevier Ltd. All rights reserved.
Published: 2006
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28. Successful in vitro cultivation of Borrelia duttonii and its comparison with Borrelia recurrentis

Author: Department of Medical Microbiology, Charing Cross Hospital, Department of Histopathology, Charing Cross Hospital, 福山大学薬学部, The Wellcome Trust Centre for the Epidemiology of Infectious Disease, University of Oxford, Mvumi Hospital, and FACULTY OF PHARMACY & PHARMACEUTICAL SCIENCES FUKUYAMA UNIVERSITY
Published: 2000

29. Borrelia recurrentis Characterization and Comparison with Relapsing-Fever, Lyme-Associated, and Other Borrelia spp

Author: 発表論文抄録, 福山大学薬学部, Department of Medical Microbiology, Charing Cross Hospital, London, United Kingdom, Department of Histopathology, Charing Cross Hospital ,London, United Kingdom, FACULTY OF PHARMACY & PHARMACEUTICAL SCIENCES FUKUYAMA UNIVERSITY, Department of Internal Medicine, Black Lion Hospital, Addis Ababa, Ethiopia, and Centre for Tropical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Abstract: シラミ媒介性回帰熱の起因菌であるBorrelia recurrentisは、これまで培養が不可能であったことからその性状はあまり知られていない。我々はシラミ媒介性回帰熱の患者から18株のボレリアの培養に成功し、これら分離株の性状について検討した。電子顕微鏡像、G+C含量、DNA相同性、鞭毛遺伝子あるいは16SrRNA遺伝子の塩基配列、SDS-PAGE、PFGEによる解析を行い、回帰熱ボレリア、ライム病関連ボレリア、その他ボレリア属に属する種との比較を行った。, Borrelia recurrentis, the cause of louse-borne relapsing fever, has until recently been considered noncultivable, which has prevented characterization of this spirochete. We successfully cultivated 18 strains from patients with louse-borne relapsing fever and present the initial characterization of these isolates. Electon microscopy revealed spirochetal cells with pointed ends, an average wavelength of 1.8 μm, an amplitude of 0.8μm, and 8 to 10 periplasmic flagella. The G+C ratio was 28.4 mol%. Whole DNA-DNA hybridizations showed similarity between the isolates of B. recurrentis but not with Borrelia hermsii, Borrelia parkeri, Borrelia turicatae, or the Lyme-associated borreliae. Sequencing studies of both the flagellin and 16S rRNA genes revealed that the greatest similarity was between B. recurrentis and Borrelia duttonii. Analysis of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of strains revealed four groups based on the position of a major protein band (one of the groups showed some heterogeneity and was subdivided into four subgroups). Pulsed-field gel electrophoresis revealed five distinct patterns.
Published: 1998

30. Cancer classification using the Immunoscore: a worldwide task force

Author: Iris D. Nagtegaal, Paul Waring, Michael I. Nishimura, Richard Palmqvist, Carlo Bifulco, Yutaka Kawakami, Christian H. Ottensmeier, Alessandro Lugli, Christoph Huber, Réjean Lapointe, Lotfi Chouchane, Noriyuki Sato, Helen K. Angell, Scott Kopetz, Kyogo Itoh, Michele Maio, Yili Wang, Bernard A. Fox, Thomas F. Gajewski, Christine Lagorce, Franck Pagès, Cedrik M. Britten, Ena Wang, Giuseppe Masucci, Patricia Shaw, Frank A. Sinicrope, Jill O'Donnell-Tormey, Fabiana Tatangelo, Andreas Lundqvist, Heinz Zwierzina, James P. Allison, Toshihiko Torigoe, P. Patel, Inti Zlobec, Blaise Clarke, Martin Asslaber, Corrado D'Arrigo, Shoichi Hazama, Martin C. Mihm, Harpreet Singh-Jasuja, Luigi Laghi, Anne Berger, Jérôme Galon, Samir N. Khleif, Paolo Delrio, Shilin N. Shukla, Gerardo Botti, Hartmann Arndt, Francesco M. Marincola, Leif Håkansson, Paolo A. Ascierto, Robert E. Hawkins, Bradly G. Wouters, Sacha Gnjatic, Graham Pawelec, Fabio Grizzi, Fernando Vidal-Vanaclocha, Shuji Ogino, Sebastian Kreiter, Kiyotaka Okuno, Peter Gibbs, Magdalena Thurin, Giorgio Trinchieri, Pamela S. Ohashi, Radiotherapie, RS: GROW - School for Oncology and Reproduction, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance Publique-Hopitaux de Paris, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Society for Immunotherapy of Cancer, Milwaukee, Infectious Disease and Immunogenetics Section (IDIS), Clinical Center and trans-NIH Center for Human Immunology (CHI), Cancer Diagnosis Program, National Cancer Institute ( NIH ), Oncology - Pathology - Anatomy, Institute of Pathology-University of Bern, Department of Pathology, Providence Portland Medical Center, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G.Pascale', TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Weill Medical College of Cornell University [New York], Colorectal Surgery Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, University of Erlangen, Institute of Pathology, Medical University Graz, Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Department of Oncology-Pathology, Karolinska Institutet [Stockholm], Harvard Medical School and Massachusetts General Hospital, Boston, CEU-San Pablo University School of Medicine and HM-Hospital of Madrid Scientific Foundation, Institute of Applied Molecular Medicine (IMMA), Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, University of Lund, Immatics Biotechnologies GmbH, Experimental Cancer Medicine Centre, University of Southampton Faculty of Medicine, Department Haematology and Oncology, Innsbruck Medical University [Austria] ( IMU ), Molecular Gastroenterology and Department of Gastroenterology, Istituto Clinico Humanitas [Milan] ( IRCCS Milan ), Humanitas University [Milan] ( Hunimed ) -Humanitas University [Milan] ( Hunimed ), Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Princess Margaret Hospital, Departments of Laboratory Medicine, Pathobiology & Radiation Oncology, Division of Cellular Signaling, Institute for Advanced Medical Research, Department of Digestive Surgery and Surgical Oncology, Yamaguchi University [Yamaguchi], Department of Surgery, Kinki University, Cancer Research Institute, New York, Avicenne Hospital, Center for Medical Research, Eberhard Karls Universität Tübingen, Oncology Institute, Loyola University Medical Center ( LUMC ), School of Cancer and Imaging Sciences, University of Manchester [Manchester], Research Center, University Hospital, Department of Oncology-Pathology [Karolinska Institutet], Georgia Health Sciences University Cancer Center, Augusta University, Brigham and Women's Hospital [Boston], Department of Medical Oncology, Royal Melbourne Hospital, University of Melbourne, Sapporo Medical University School of Medicine, Department of Immunology and Immunotherapy, Kurume University School of Medicine, The Gujarat Cancer & Research Institute, Asarwa, Department of Medical Biosciences, Pathology, Pathology Department, Radboud University Medical Center [Nijmegen], Institute for Cancer Research, Center of Translational medicine, Department of Histopathology, Dorset County Hospital, MD Anderson Cancer Center, Houston, Mayo Clinic and Mayo College of Medicine, Rochester, Cancer Inflammation Program, Center for Cancer Research, Oncology and Hematology, University of Chicago, Medical Oncology and Innovative Therapies Unit, Fondazione Melanoma Onlus, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute-Robert W. Franz Cancer Center, Department of Molecular Microbiology and Immunology, Oregon Health and Science University, BMC, Ed., Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Harvard Medical School [Boston] (HMS), Memorial Sloane Kettering Cancer Center [New York], Lund University [Lund], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), University of Toronto-University of Toronto, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Loyola University Medical Center (LUMC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), University System of Georgia (USG)-University System of Georgia (USG), Sapporo Medical University-Sapporo Medical University, Kurume University-Kurume University, Oregon Health and Science University [Portland] (OHSU), Université Paris Descartes - Paris 5 (UPD5)-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), Innsbruck Medical University [Austria] (IMU), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)
Subjects: Oncology, medicine.medical_specialty, Medicin och hälsovetenskap, Internationality, Colorectal cancer, Advisory Committees, lcsh:Medicine, Review, Medical and Health Sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Tumor Microenvironment, medicine, Humans, Stage (cooking), Biomarker discovery, 030304 developmental biology, Medicine(all), 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Merkel cell carcinoma, business.industry, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, Cancer, General Medicine, Classification, medicine.disease, Primary tumor, 3. Good health, Treatment Outcome, Tumor progression, 030220 oncology & carcinogenesis, Immunology, Biomarker (medicine), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the 'Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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31. Data set for reporting of peripheral neuroblastic tumours: recommendations from the international collaboration on cancer reporting (ICCR).

Author: Jarzembowski JA, Webster F, Beiske K, Cohn SL, de Krijger RR, Irwin MS, Navarro S, Okita H, Shimada H, Stahlschmidt J, Vokuhl C, Wang LL, Cohen M, and Reyes-Mugica M
Abstract: Peripheral neuroblastic tumours are the most common extracranial solid neoplasms occurring in children. Proper classification is critical for directing therapy and predicting prognosis. Nonetheless, their relative rarity makes accurate pathological assessment challenging, even for experienced pathologists. Here we report on a new international data set for the pathology reporting of biopsy and resection specimens with peripheral neuroblastic tumours. The data set was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. According to the ICCR's process for data set development, an international expert panel consisting of paediatric pathologists and oncologists produced a set of core and non-core data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were neuroblastic tumour experts affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element, its clinical relevance and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the data sets, including a synoptic reporting guide, were published on the ICCR website. This first international data set for paediatric peripheral neuroblastic tumours is intended to promote high-quality, standardised pathology reporting. Its widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication and enhance comparability of data, all of which will help to improve management of children with peripheral neuroblastic tumours., (© 2025 John Wiley & Sons Ltd.)
Published: 2025
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32. Acquired comedonal plaques in a middle-aged woman.

Author: Chung JG, Wilsher MJ, Calonje E, Magdalinou N, Mummery C, Hussain K, and Roberts N
Abstract: Competing Interests: Conflicts of interest: The authors declare they have no conflicts of interest.
Published: 2025
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33. Recurrent balanoposthitis and oral blistering in a young man.

Author: Chung JG, Gupta G, Wilsher MJ, Mee JB, Setterfield J, and Bunker CB
Abstract: Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.
Published: 2025
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34. Molecular profiling of a cohort with epidermolysis bullosa in India: a single centre experience.

Author: Kumar A, Jamwal M, Gupta S, Sharma R, Singh N, Kaushal L, Kumar S, Kumar V, Behera B, De D, Handa S, Nahar U, Chatterjee D, Das R, and Mahajan R
Subjects: Humans, India epidemiology, Male, Female, Child, Child, Preschool, Adolescent, Infant, Adult, Young Adult, Phenotype, Mutation, Genotype, Epidermolysis Bullosa, Junctional genetics, Epidermolysis Bullosa, Junctional pathology, Keratin-5 genetics, Keratin-14 genetics, Epidermolysis Bullosa Dystrophica genetics, Cohort Studies, Middle Aged, Epidermolysis Bullosa Simplex genetics, Epidermolysis Bullosa Simplex pathology, Epidermolysis Bullosa genetics
Abstract: Background: Epidermolysis bullosa (EB) encompasses rare hereditary skin conditions marked by skin fragility, nail dystrophy and minor trauma-induced skin blisters., Objectives: To identify genetic variants in patients with EB in India and to examine the relationship between genotypic and phenotypic manifestations., Methods: Patients with EB seen consecutively over a period of 5 years at an outpatient department of dermatology (Postgraduate Institute of Medical Education and Research, Chandigarh, India) were included in the study. Baseline demographic data, birth history, family history, skin manifestations at birth, medical history, current cutaneous manifestations and the evolution of the disease were assessed and recorded. Genetic variants were identified using targeted gene panel sequencing for 23 EB-related genes and a genetic-phenotype analysis was performed., Results: Our study included 65 patients with EB. Among these 65 patients with EB, 38 had dystrophic EB (DEB, 58%), 12 had junctional EB (JEB, 18%), 12 had EB simplex (EBS, 18%) and 3 had Kindler EB (KEB, 5%). Dominant and recessive forms of dystrophic EB accounted for 17% (n = 11) and 42% (n = 27), respectively, of the 65 individuals with EB. We identified 75 genetic variants, 59% (n = 44) newly discovered and 41% (n = 31) previously reported. Compound heterozygous variants were more frequent (56%; 15/27) than homozygous ones (44%; 12/27) in individuals with recessive DEB. Patients with JEB harboured LAMB3 mutations more frequently, whereas patients with EBS harboured KRT5 and KRT14 missense heterozygous mutations. Patients with KEB had homozygous mutations in FERTM1., Conclusions: Our study has unveiled several novel genetic variants and severe phenotypes associated with nonsense genetic variants. These findings offer valuable insights for future clinical assessments and tailored management strategies., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2025
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35. General dermatology and dermatology in primary healthcare.

Author: Sutton JE, Qureshi U, White N, Body S, Byrom R, Bateman AC, and Pearson IC
Abstract: Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.
Published: 2025
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36. Mistakes to avoid in the management of abdominal tuberculosis.

Author: Chatterjee A, Jha DK, Sekar A, and Sharma V
Abstract: Introduction: The diagnosis and management of abdominal tuberculosis, i.e Gastrointestinal Tuberculosis (GITB) and tuberculous peritonitis (TBP) is challenging. Abdominal tuberculosis, presenting usually with abdominal pain, intestinal obstruction, and constitutional symptoms, is typically a paucibacillary condition. The diagnosis hinges on a correct interpretation of clinical, radiological, histological, biochemical, and microbiological findings as also appropriately assessing response to therapy., Areas Covered: The authors review potential missteps that could occur in managing GITB and TBP sourced from published literature and clinical experience. These include avoiding excess use of tests with limited accuracy, understanding limitations of ascitic adenosine deaminase (ADA) and granulomas, avoiding empirical antitubercular therapy (ATT) where possible but also understanding that microbiological tests may not always be positive, and finally not to bank solely on subjective clinical responses but to use objective markers in assessing response to therapy. In addition, diagnosis of predisposing immunosuppressed states, attention to nutrition, appropriate management of sequelae with endoscopic dilatation/surgery, and early surgery when indicated are some of the additional issues discussed., Expert Opinion: In future, a more secure diagnosis banking on the use of better microbiological tools, multiparameter-based models, artificial intelligence-based approaches, and use of advances in -omics-based approaches can improve diagnosis and avoid some missteps.
Published: 2025
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37. Verrucous plaque over leg in a young male.

Author: Meghana KB, Sharma A, Chatterjee D, and Narang T
Published: 2025
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38. Endoscopic ultrasound guided liver biopsy and portal pressure gradient: when, why and how? Can it become the standard of care in endo-hepatology?

Author: Dhar J, Yadav A, Mitra S, Nabi Z, Aggarwal M, Gupta P, Facciorusso A, Crinò SF, Trikudanathan G, and Samanta J
Abstract: Introduction: The armamentarium of 'Endo-hepatology' is proliferating with the advancements in techniques and availability of new devices in the field of endoscopic ultrasound (EUS). This has resulted in the merger of multitude of diagnostic and therapeutic interventions, such as EUS-liver biopsy (LB), EUS-angioembolization of gastric varices, EUS-portal pressure gradient (PPG) measurement, and others into a 'one-stop-shop' for efficient patient management. Lack of standardization of these techniques form a major hinderance in their widespread adoption., Areas Covered: A comprehensive literature search was undertaken across various databases on EUS-LB and EUS-PPG till November 2024 for reviews, observational studies, and randomized trials on EUS-LB and EUS-PPG, describing its indications, technique, and data of safety and efficacy, detailing its role in day-to-day clinical practice., Expert Opinion: EUS-LB and EUS-PPG have shown promise in the ever-growing field of endo-hepatology. EUS-LB has exhibited excellent safety profile and comparable tissue yield compared to its percutaneous counterpart. On the other hand, EUS-PPG seems to be a viable alternative although it needs to be standardized further. From a patient and hospital perspective, they might prove to be convenient and cost effective. Nevertheless, more evidence is warranted before they can be labeled as the new standard of care.
Published: 2025
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39. Human-correlated genetic models identify precision therapy for liver cancer.

Author: Müller M, May S, Hall H, Kendall TJ, McGarry L, Blukacz L, Nuciforo S, Georgakopoulou A, Jamieson T, Phinichkusolchit N, Dhayade S, Suzuki T, Huguet-Pradell J, Powley IR, Officer-Jones L, Pennie RL, Esteban-Fabró R, Gris-Oliver A, Pinyol R, Skalka GL, Leslie J, Hoare M, Sprangers J, Malviya G, Mackintosh A, Johnson E, McCain M, Halpin J, Kiourtis C, Nixon C, Clark G, Clark W, Shaw R, Hedley A, Drake TM, Tan EH, Neilson M, Murphy DJ, Lewis DY, Reeves HL, Le Quesne J, Mann DA, Carlin LM, Blyth K, Llovet JM, Heim MH, Sansom OJ, Miller CJ, and Bird TG
Abstract: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer-related mortality worldwide 1,2 . HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulate progressive driver mutations 3 , with hepatocytes the most likely cell of origin 2 . However, the landscape of driver mutations in HCC is broadly independent of the underlying aetiologies 4 . Despite an increasing range of systemic treatment options for advanced HCC, outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations 5,6 . Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC 7 . Here we generated a suite of genetically driven immunocompetent in vivo and matched in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance and metastasis. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with the human histopathology. In a proof-of-principle analysis, we verified response to standard-of-care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not previously been linked to HCC treatment. Cladribine acts in a highly effective subtype-specific manner in combination with standard-of-care therapy., Competing Interests: Competing interests: Material for the lenvatinib day 15 and day 30 timepoint experiments (Fig. 4h–j) was provided by Eisai. AZD2171 was provided by AstraZeneca. D.A.M. is a director, shareholder and employee of FibroFind. L.M.C. has consulted for Ono Pharmaceuticals UK on unrelated work. J.M.L. is receiving research support from Eisai Inc and Bayer Pharmaceuticals; is consulting and performing sponsored lectures for Eisai Inc., Merck, Roche, Genentech, AstraZeneca, Bayer Pharmaceuticals, AbbVie, Sanofi, Moderna, Glycotest and Exelixis; and participates in the Data Safety Monitoring Board for Bristol Myers Squibb. The other authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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40. Primary Angiitis of the Central Nervous System Masquerading as a Pontine Glioma.

Author: Kataria M, Salunke P, Mishra K, Gupta K, and Chakravarty K
Published: 2025
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41. Development and validation of BCG vaccine-induced novel granulomatous liver injury preclinical animal model.

Author: Sharma S, Moudgil A, Grewal J, Khatri P, Sharma V, Premkumar M, Bal A, Banerjee D, and Patil AN
Abstract: Background: Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB (tuberculosis) and autoimmune granulomatous liver diseases. Antitubercular (ATT) and other drugs' metabolism in the presence of a specific type of liver injury is not well understood. The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG (Bacillus Calmette-Guérin) vaccine, further studying it in the presence of ATT dosing, and analyze the pharmacokinetics of isoniazid, rifampicin, and their respective primary metabolites., Methods: We used 56 rats in seven equal groups. Group I functioned as a normal control (NC) receiving normal saline only. Groups II-IV received intravenous injections of low-, medium-, and high-dose BCG vaccine daily for 21 days. Groups V, VI, and VII received isoniazid (H) alone, rifampicin (R) alone, and isoniazid + rifampicin(HR) for a subsequent 15 days in addition to high dose BCG for the first 21 days, respectively. Liver function tests (LFT) were monitored on days 0, 21, 28, and 36. Rats were sacrificed later for oxidative stress and histopathological examination., Results: The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21 (p < 0.05). Isoniazid, rifampicin, and combination intervention groups demonstrated normalization of the BCG-led LFT changes. Histology and oxidative stress parameters confirmed model development and biochemical changes. Isoniazid area under the curve (AUC) showed a reduction of 16.9% in BCG + HR group in comparison to the BCG + H group (p = 0.01). Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG + HR group in comparison to the BCG + R group (p = 0.001)., Conclusion: A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response., (© 2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)
Published: 2025
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42. Approach to the Paediatric Patient With Suspected Pheochromocytoma or Paraganglioma Versus Neuroblastoma.

Author: Hendriks AEJ, Burns C, Fleming B, Harper I, Hook E, Armstrong R, Pamporaki C, Eisenhofer G, Murray MJ, and Casey RT
Subjects: Humans, Diagnosis, Differential, Male, Child, Female, Child, Preschool, Pheochromocytoma diagnosis, Pheochromocytoma pathology, Neuroblastoma diagnosis, Neuroblastoma pathology, Adrenal Gland Neoplasms diagnosis, Adrenal Gland Neoplasms pathology, Paraganglioma diagnosis, Paraganglioma pathology, Paraganglioma diagnostic imaging
Abstract: Catecholamine-producing tumors of childhood include neuroblastic tumors, phaeochromocytoma, and paraganglioma (PPGL). PPGL and neuroblastic tumors can arise in similar anatomical locations and clinical presentations can overlap, resulting in diagnostic challenges. Distinguishing between these tumor types is critical as management and long-term surveillance strategies differ depending on the diagnosis. Herein we describe 2 clinical cases and illustrate key considerations in the diagnostic workup of a neuroblastoma vs PPGL for patients presenting with adrenal, pelvic, and retroperitoneal masses in childhood., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Published: 2025
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43. Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients.

Author: Ali RH, Almanabri M, Ali NY, Alsaber AR, Khalifa NM, Hussein R, Alateeqi M, Mohammed EMA, Jama H, Almarzooq A, Benobaid N, Alqallaf Z, Ahmed AA, Bahzad S, and Almurshed M
Subjects: Humans, Child, Adult, Male, Adolescent, Female, Child, Preschool, Retrospective Studies, Young Adult, Middle Aged, Infant, Aged, Aged, 80 and over, Mutation, MAP Kinase Signaling System genetics, Kuwait, Biomarkers, Tumor genetics, Proto-Oncogene Proteins B-raf genetics, Glioma genetics, Glioma pathology, Brain Neoplasms genetics, Brain Neoplasms pathology
Abstract: Aims: Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait., Methods: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations., Results: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs., Conclusion: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)
Published: 2025
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44. Skull fractures or accessory sutures: A case report.

Author: Sabu R, I'Ons B, and Mangham DC
Abstract: Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interest concerning this article.
Published: 2025
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45. Increasing the number of minor salivary glands from patients with Sjögren's disease improves the diagnostic and measurement precision of the histological focus score.

Author: Tryposkiadis K, Nayar S, Pucino V, Smith CG, Brown RM, Bates T, Bowman SJ, Sitch A, Price M, Barone F, Deeks J, and Fisher BA
Abstract: Objectives: Minor salivary gland (MSG) biopsy has an important role in Sjögren's disease diagnosis and research. MSGs show within-patient variation in number of lymphocytic foci per unit area, but the optimal number of MSGs required to balance reproducibility and clinical acceptability has not been determined., Methods: Monte Carlo simulations were performed to investigate impact of MSG number on (i) diagnosis based on focus score (FS) ≥1; (ii) reproducibility, defined as the extent to which 2 FS measurements obtained from 2 within-patient biopsies are the same, assuming no systematic differences have occurred in between biopsies; and (iii) smallest sample size required to detect a clinically meaningful difference in FS. Data simulation was repeated for different MSG numbers (range, 2-7)., Results: Higher reproducibility was noted for every unit increase in MSG number, with the median absolute difference between 2 within-patient FS measurements decreasing from 1.05 (SD = 0.25) with 2 glands to 0.52 (SD = 0.12) with 7 glands. MSG number influenced the probability of a simulated patient receiving a FS ≥1, increasing from a median of 0.67 with 2 glands to 0.77 with ≥5 glands. MSG number influenced clinical trial sample sizes. For example, 80% statistical power to detect a 40% FS reduction required a sample size per group of 62 with 2 glands and 25 with 7 glands., Conclusions: For a diagnostic threshold of FS ≥1, a minimum of 5 glands should ideally be targeted. For continuous FS values, a larger number of MSGs (eg, 6) will increase reproducibility further and reduce clinical trial sample size requirements., Competing Interests: Competing interests BAF has undertaken consultancy for Novartis, BMS, Servier, Galapagos, Roche, UCB, Sanofi, Janssen, AstraZeneca, Otsuka, Amgen, and Kiniksa and received research funding from Janssen, Servier, Galapagos, and Celgene. SJB has undertaken consultancy on SjD in the past 3 years for: AbbVie, Amgen, Argenx, Aurinia, Bain, BMS, EcoR1, Iqvia, J&J/Janssen, Kiniksa, and Novartis. FB is a current employee of Candel Therapeutics. KT, SN, VP, CGS, RMB, TB, AS, MP, and JD have nothing to declare., (Copyright © 2025. Published by Elsevier B.V.)
Published: 2025
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46. Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia.

Author: Golwala ZM, Goncalves HS, Moirangthem RD, Evans G, Lizot S, de Koning C, Garrigue A, Corredera MM, Ocampo-Godinez JM, Howley E, Kricke S, Awuah A, Obiri-Yeboa I, Rai R, Sebire N, Bernard F, De Braem VBC, Boztug K, Cole T, Gennery AR, Hackett S, Hambleton S, Holm M, Kusters MA, Klocperk A, Marzollo A, Marcus N, Nademi Z, Schmid JP, Pichler H, Sellmer A, Soler-Palacin P, Soomann M, Torpiano P, van Montfrans J, Nierkens S, Adams S, Buckland M, Gilmour K, Worth A, Thrasher AJ, Davies EG, André I, and Kreins AY
Abstract: Persistent selective T-lymphocytopaenia is found both in SCID and congenital athymia. Without molecular diagnosis, it is challenging to determine whether HCT or thymus transplantation ought to be performed. Ex vivo T-lymphopoiesis assays have been proposed to assist clinical decision-making for genetically undefined patients. We investigated 20 T-lymphocytopaenic patients, including 13 patients awaiting first-line treatment and 7 patients with failed immune reconstitution after previous HCT or thymus transplantation. Whilst developmental blocks in ex vivo T-lymphopoiesis indicated haematopoietic cell-intrinsic defects, successful T-lymphocyte differentiation required careful interpretation, in conjunction with clinical status, immunophenotyping, and genetic investigations. Of the 20 patients, 13 proceeded to treatment, with successful immune reconstitution observed in 4 of the 6 patients post-HCT and 4 of the 7 patients after thymus transplantation, the latter including two patients who had previously undergone HCT. Whilst further validation and standardization are required, we conclude that assessing ex vivo T-lymphopoiesis during the diagnostic pathway for genetically undefined T-lymphocytopaenia improves patient outcomes by facilitating corrective treatment choice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)
Published: 2025
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47. The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development.

Author: Suntharalingham JP, Del Valle I, Buonocore F, McGlacken-Byrne SM, Brooks T, Ogunbiyi OK, Liptrot D, Dunton N, Madhan GK, Metcalfe K, Nel L, Marshall AR, Ishida M, Sebire NJ, Moore GE, Crespo B, Solanky N, Conway GS, and Achermann JC
Subjects: Humans, Female, Pregnancy, Fetal Development genetics, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Fetus metabolism, Gene Expression Regulation, Developmental, Turner Syndrome genetics, Placenta metabolism, Transcriptome, Chromosomes, Human, X genetics, Monosomy genetics
Abstract: Monosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore undertook an exploratory study of the transcriptomic landscape of clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) with matched 46,XX and 46,XY control samples between 11 and 15 weeks post conception (n = 78). Although most pseudoautosomal region 1 (PAR1) genes are lower in monosomy X tissues, we also found reduced expression of several key genes escaping X inactivation (e.g., KDM5C and KDM6A), several ancestral X-Y gene pairs, and potentially clinically important transcripts such as genes implicated in ascending aortic aneurysm. In contrast, higher expression of an autosomal, long non-coding RNA (OVCH1-AS1) is seen in all 45,X tissues. In the placenta, lower expression of CSF2RA is demonstrated, likely contributing to immune dysregulation. Taken together, these findings provide insights into the biological consequences of a single X chromosome during early human development and potential insights in genetic mechanisms in Turner syndrome., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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48. MEK Inhibition With Trametinib for the treatment of MAP2K1-Mutated Rosai-Dorfman-Destombes Disease Arising from the Nasopharynx in a Paediatric Patient.

Author: Cuerden C, Alsalem M, Sproson E, Burgess A, Jogai S, Portess H, Deem K, Ismail-Koch H, Abla O, and Bate J
Published: 2025
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49. Isolated Cerebral Myeloid Sarcoma in an Allogeneic Stem Cell Transplant Recipient.

Author: Magliano G, Zanon S, de Domenico R, Galli M, Morello E, Lorenzi L, Paolino G, Fontanella M, Buttolo L, Bertoli D, Biasiotto G, Malagola M, Marnoni R, Farina M, Radici V, Bernardi S, Leoni A, Russo D, and Avenoso D
Published: 2025
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50. A retrospective analysis of placental histopathological findings in gestational diabetes mellitus (GDM).

Author: Byrne J, Ranaei-Zamani N, Hutchinson JC, and Hillman S
Abstract: Introduction: The placenta plays a pivotal role in supporting fetal growth and disruptions in its development and function can impact fetal outcomes. While placental pathology has been extensively studied in clinical conditions such as pre-eclampsia and fetal growth restriction (FGR), the association between placental abnormalities and gestational diabetes mellitus (GDM) is still unclear. This study aims to explore the placental pathology associated with GDM, shedding light on potential links to adverse perinatal outcomes., Methods: A retrospective cohort study was conducted using electronic patient data from the Fetal Medicine and Neonatal Units at University College London Hospital. Placental samples were obtained and analysed at Great Ormond Street Hospital. Maternal demographics, obstetric history and placental histopathology were reviewed. Statistical analyses were performed to identify associations and risk factors., Results: Of the 2580 pregnancies analysed, 341 were GDM pregnancies, 549 had FGR and 66 had both GDM and FGR. GDM pregnancies required increased rates of obstetric intervention and neonatal care admission. Placental pathology in GDM revealed a higher prevalence of maternal vascular malperfusion (MVM) lesions, whilst GDM-related FGR showed further associations with MVM lesions and adverse perinatal outcomes., Discussion: Our study highlights MVM lesions as a prominent feature in the placentas of GDM pregnancies, especially when associated with FGR. These lesions are linked to adverse perinatal outcomes, emphasizing the need for enhanced antenatal care in these cases. The study contributes insights into the complex relationship between GDM, placental pathology and adverse fetal outcomes, laying the foundation for future investigations into early interventional strategies., Competing Interests: Declaration of competing interest None., (Copyright © 2025. Published by Elsevier Ltd.)
Published: 2025
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