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3 results on '"Molecular Gastroenterology and Department of Gastroenterology"'

1. 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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2. The "unnatural" history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance.

Author

Ahadova A, Seppälä TT, Engel C, Gallon R, Burn J, Holinski-Feder E, Steinke-Lange V, Möslein G, Nielsen M, Ten Broeke SW, Laghi L, Dominguez-Valentin M, Capella G, Macrae F, Scott R, Hüneburg R, Nattermann J, Hoffmeister M, Brenner H, Bläker H, von Knebel Doeberitz M, Sampson JR, Vasen H, Mecklin JP, Møller P, and Kloor M

Subjects
Colorectal Neoplasms genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, DNA Mismatch Repair genetics, DNA Repair Enzymes genetics, Humans, Mass Screening methods, Microsatellite Instability, Risk Factors, Colonoscopy methods, Colorectal Neoplasms diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Population Surveillance methods
Abstract

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Published
2021
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3. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.

Author

Pagès F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, Lugli A, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Börger E, Hartmann A, Geppert C, Kolwelter J, Merkel S, Grützmann R, Van den Eynde M, Jouret-Mourin A, Kartheuser A, Léonard D, Remue C, Wang JY, Bavi P, Roehrl MHA, Ohashi PS, Nguyen LT, Han S, MacGregor HL, Hafezi-Bakhtiari S, Wouters BG, Masucci GV, Andersson EK, Zavadova E, Vocka M, Spacek J, Petruzelka L, Konopasek B, Dundr P, Skalova H, Nemejcova K, Botti G, Tatangelo F, Delrio P, Ciliberto G, Maio M, Laghi L, Grizzi F, Fredriksen T, Buttard B, Angelova M, Vasaturo A, Maby P, Church SE, Angell HK, Lafontaine L, Bruni D, El Sissy C, Haicheur N, Kirilovsky A, Berger A, Lagorce C, Meyers JP, Paustian C, Feng Z, Ballesteros-Merino C, Dijkstra J, van de Water C, van Lent-van Vliet S, Knijn N, Mușină AM, Scripcariu DV, Popivanova B, Xu M, Fujita T, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Sargent DJ, Fox BA, and Galon J

Subjects
Adult, Aged, Colonic Neoplasms immunology, Female, Humans, Lymphocytes, Tumor-Infiltrating, Male, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Reproducibility of Results, Colonic Neoplasms classification, Colonic Neoplasms diagnosis, Neoplasm Recurrence, Local etiology
Abstract

Background: The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer., Methods: An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrell's C-statistics was used to assess model performance., Findings: Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0·97 for colon tumour; r=0·97 for invasive margin; p<0·0001). In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (14 [8%] patients with a high Immunoscore vs 65 (19%) patients with an intermediate Immunoscore vs 51 (32%) patients with a low Immunoscore; hazard ratio [HR] for high vs low Immunoscore 0·20, 95% CI 0·10-0·38; p<0·0001). The findings were confirmed in the two validation sets (n=1981). In the stratified Cox multivariable analysis, the Immunoscore association with time to recurrence was independent of patient age, sex, T stage, N stage, microsatellite instability, and existing prognostic factors (p<0·0001). Of 1434 patients with stage II cancer, the difference in risk of recurrence at 5 years was significant (HR for high vs low Immunoscore 0·33, 95% CI 0·21-0·52; p<0·0001), including in Cox multivariable analysis (p<0·0001). Immunoscore had the highest relative contribution to the risk of all clinical parameters, including the American Joint Committee on Cancer and Union for International Cancer Control TNM classification system., Interpretation: The Immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer. These results support the implementation of the consensus Immunoscore as a new component of a TNM-Immune classification of cancer., Funding: French National Institute of Health and Medical Research, the LabEx Immuno-oncology, the Transcan ERAnet Immunoscore European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, Institut National du Cancer, Italian Association for Cancer Research, national grants and the Society for Immunotherapy of Cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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