Lydia Lartigue1, Agnès Neuville1, Pauline Lagarde1, Céline Brulard2, Piotr Rutkowski3, Paolo Dei Tos4, Eva Wardelmann5, Maria Debiec-Rychter6, Antoine Italiano1, Jean-Michel Coindre1, Frédéric Chibon7. 1. Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France; Bordeaux University, 146 rue Léo Saignat, F-33000 Bordeaux, France. 2. Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France. 3. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland. 4. Department of Anatomic Pathology, Treviso General Hospital, Piazza Ospedale 1, 31100 Treviso, Italy. 5. Universitätsklinikum Münster, Gerhard-Domagk-Institut für Pathologie, Albert-Schweitzer-Campus 1, Gebäude D17, Domagkstraße 17, 48149 Münster, Germany. 6. Department of Human Genetics, KU Leuven and University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. 7. Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France. Electronic address: f.chibon@bordeaux.unicancer.fr.
Abstract
PURPOSE: Imatinib mesylate is the front-line targeted therapy for gastrointestinal stromal tumours (GISTs). Patient's eligibility to adjuvant imatinib after primary tumour resection is currently based on histological and clinical risk assessment. While therapeutic options are clear for the very-low, low and high-risk subpopulations, no standard is actually available for the tumours classified as intermediate. Since we recently validated genomic index (GI), a measure of the level of genomic alterations, as a strong predictor of clinical outcome in GIST, we asked whether it could also represent a novel prognostic factor for the intermediate subgroup. EXPERIMENTAL DESIGN: 82 intermediate risk patients were selected based on the Armed Forces Institute of Pathology (AFIP) classification for genomic profiling. RESULTS: Data revealed that even if studied samples generally harboured a combination of the typical genetic aberrations found in GIST, i.e. 1p, 14q 22q deletions and frequently lost CDKN2A locus on chromosome 9, they profoundly differed from each other on the total number of genomic changes and GI value. Kaplan-Meier analyses of metastatic-free survival unveiled that stratification of the tumours by the GI value at a cutoff of 10 separated the good from the poor prognosis patients, proven that metastatic-risk in GIST intermediate patients is strongly associated with high GI values and genome complexity. CONCLUSION: GI is validated here as a robust marker to predict intermediate-GIST clinical outcome. Applicable in numerous Pathology Laboratories already using array comparative genomic hybridisation (CGH) with formalin-fixed paraffin-embedded (FFPE) samples, this assay presently stands as an efficient tool for the clinical management of intermediate GIST-patients.
PURPOSE:Imatinib mesylate is the front-line targeted therapy for gastrointestinal stromal tumours (GISTs). Patient's eligibility to adjuvant imatinib after primary tumour resection is currently based on histological and clinical risk assessment. While therapeutic options are clear for the very-low, low and high-risk subpopulations, no standard is actually available for the tumours classified as intermediate. Since we recently validated genomic index (GI), a measure of the level of genomic alterations, as a strong predictor of clinical outcome in GIST, we asked whether it could also represent a novel prognostic factor for the intermediate subgroup. EXPERIMENTAL DESIGN: 82 intermediate risk patients were selected based on the Armed Forces Institute of Pathology (AFIP) classification for genomic profiling. RESULTS: Data revealed that even if studied samples generally harboured a combination of the typical genetic aberrations found in GIST, i.e. 1p, 14q 22q deletions and frequently lost CDKN2A locus on chromosome 9, they profoundly differed from each other on the total number of genomic changes and GI value. Kaplan-Meier analyses of metastatic-free survival unveiled that stratification of the tumours by the GI value at a cutoff of 10 separated the good from the poor prognosis patients, proven that metastatic-risk in GIST intermediate patients is strongly associated with high GI values and genome complexity. CONCLUSION: GI is validated here as a robust marker to predict intermediate-GIST clinical outcome. Applicable in numerous Pathology Laboratories already using array comparative genomic hybridisation (CGH) with formalin-fixed paraffin-embedded (FFPE) samples, this assay presently stands as an efficient tool for the clinical management of intermediate GIST-patients.
Authors: Keith M Skubitz; Kate Geschwind; Wayne W Xu; Joseph S Koopmeiners; Amy P N Skubitz Journal: J Transl Med Date: 2016-02-13 Impact factor: 5.531
Authors: Daniel Orbach; Véronique Mosseri; Daniel Pissaloux; Gaelle Pierron; Bernadette Brennan; Andrea Ferrari; Frederic Chibon; Gianni Bisogno; Gian Luca De Salvo; Camille Chakiba; Nadège Corradini; Véronique Minard-Colin; Anna Kelsey; Dominique Ranchère-Vince Journal: Cancer Med Date: 2018-03-13 Impact factor: 4.452
Authors: Michael C Heinrich; Janice Patterson; Jonathan A Fletcher; Sebastian Bauer; Carol Beadling; Yuexiang Wang; Maria Debiec-Rychter; Barbara Dewaele; Christopher L Corless; Anette Duensing; Chandrajit P Raut; Brian Rubin; Tamas Ordog; Matt van de Rijn; Jerry Call; Thomas Mühlenberg Journal: Clin Sarcoma Res Date: 2019-03-05
Authors: Jan Köster; Paul Piccinelli; Linda Arvidsson; Fredrik Vult von Steyern; Camila Bedeschi Rego De Mattos; Martin Almquist; Jenny Nilsson; Linda Magnusson; Fredrik Mertens Journal: Lab Invest Date: 2022-03-22 Impact factor: 5.502