Br J Cancer. 2012 Aug 28. doi: 10.1038/bjc.2012.390. [Epub ahead of print]
Genomic Grade Index predicts postoperative clinical outcome of GIST.
1] Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille; UMR1068 Inserm; Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13273 Marseille Cedex 09, France  Department of Medical Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR1068 Inserm, Marseille, France  Aix-Marseille University, Marseille, France.
Background:Prognosis of localised gastrointestinal stromal tumour (GIST) is heterogeneous, notably for patients with AFIP intermediate or high risk of relapse, who are candidates to adjuvant imatinib. We hypothesised that gene expression profiles might improve the prognostication and help to refine the indications for imatinib.Methods:We collected gene expression and histoclinical data of 146 pre-treatment localised GIST samples treated with surgery alone. We searched for a gene expression signature (GES) predictive for relapse-free survival (RFS) and compared its performances to that of three published prognostic proliferation-based GES (Genomic Grade Index (GGI), 16-Kinase, and CINSARC) and AFIP classification. We also analysed a data set from 28 patients with advanced GIST treated with neo-adjuvant imatinib.Results:We identified a 275-gene GES (gene expression signature) predictive of RFS in a learning set and validated its robustness in an independent set. However, the GGI outperformed its prognostic performances, and those of the two other signatures and the AFIP intermediate-risk classification in two independent tests sets in uni- and multivariate analyses. Importantly, GGI could split the AFIP intermediate/high-risk samples into two groups with different RFS. Genomic Grade Index 'high-risk' tumours were more proliferative and genetically unstable than 'low-risk' tumours, and more sensitive to imatinib.Conclusion:GGI refines the prediction of RFS in localised GIST and might help tailor adjuvant imatinib.British Journal of Cancer advance online publication, 28 August 2012; doi:10.1038/bjc.2012.390 www.bjcancer.com.
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