1. Evaluation of KRAS , NRAS and BRAF mutational status and microsatellite instability in early colorectal carcinomas invading the submucosa (pT1): towards an in-house molecular prognostication for pathologists?
- Author
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Bourhis A, De Luca C, Cariou M, Vigliar E, Barel F, Conticelli F, Marcorelles P, Nousbaum JB, Robaszkiewicz M, Samaison L, Badic B, Doucet L, Troncone G, and Uguen A
- Subjects
- Case-Control Studies, Colorectal Neoplasms pathology, Female, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, Male, Mutation, Neoplasm Metastasis, Pathologists, Pathology, Molecular, Prognosis, Sequence Analysis, DNA, Colorectal Neoplasms diagnosis, GTP Phosphohydrolases genetics, Membrane Proteins genetics, Microsatellite Instability, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Aim: We aimed to study the prognostic value of KRAS , NRAS , BRAF mutations and microsatellite stable (MSS)/instable (MSI) in the field of colorectal cancer invading the submucosa (ie, pT1 colorectal cancer (CRC))., Methods: We led a case-control study in tumour samples from 60 patients with pT1 CRC with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for KRAS , NRAS , BRAF mutations (Idylla testing and next generation sequencing, NGS) and MSS/MSI status (Idylla testing and expression of mismatch repair (MMR) proteins using immunohistochemistry)., Results: KRAS mutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (OR=1.11 (0.38 to 3.25), p=0.8548), NRAS mutations in 1/20 (5%) cases and 3/40 (7.5%) controls (OR=3.08 (0.62 to 15.39), p=0.1698) and BRAF mutations in 3/20 (15%) cases and 6/40 (15%) controls (OR=1.00 (0.22 to 4.5), p=1.00). A MSI status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (OR=1.2353 (0.26 to 5.79), p=0.7885). Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing KRAS, NRAS and BRAF mutations (Kappa value of 0.849 (0.748 to 0.95) between Idylla and NGS) and MSS/MSI (Idylla)-proficient MMR/deficient MMR (immunohistochemistry) status (Kappa value of 1.00)., Conclusion: Although being feasible using the fully automated Idylla method as well as NGS, the molecular testing of KRAS, NRAS, BRAF and MSS/MSI status does not seem useful for prognostic purpose in the field of pT1 CRC., Competing Interests: Competing interests: Biocartis company has provided Idylla dedicated cartridges for this study but has not taken part in data interpretation or manuscript writing in this work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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