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?. Issue 11 (9th April 2020)

• Record Type: Journal Article
• Authors: Bourhis, Amélie; De Luca, Caterina; Cariou, Mélanie; Vigliar, Elena; Barel, Fanny; Conticelli, Floriana; Marcorelles, Pascale; Nousbaum, Jean-Baptiste; Robaszkiewicz, Michel; Samaison, Laura; Badic, Bogdan; Doucet, Laurent; Troncone, Giancarlo; Uguen, Arnaud
• Is Part Of: Journal of clinical pathology. Volume 73:Issue 11(2020)
• Page Start: 741
• Page End: 747
• Publication Date: 2020-04-09
• Subjects: colorectal cancer -- metastasis -- molecular pathology; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jclinpath-2020-206496
• Languages: English
• ISSNs: 0021-9746

Abstract

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.