The prognostic role of microsatellite instability, codon-specific KRAS, and BRAF mutations in colon cancer.

Abstract

This study aimed to establish a correlation between MSI, KRAS mutations, and BRAF(V600E) in colon cancer and to investigate the prognostic effect. Colon cancer patients who underwent surgical intervention were enrolled. MSI status was identified by genotyping, and the mutational statuses of KRAS and BRAF were determined by MassARRAY, targeting 22 mutations. The clinicopathological differences and correlations between these factors were analyzed. Among 1,063 patients, tumors with MSI-H were significantly associated with BRAF(V600E) (P = 0.001). KRAS and BRAF mutations were mutually exclusive (P = 0.001). Patients with MSI-H tumors had significantly improved overall survival compared with patients that had microsatellite instability-low/stable (MSI-L/MSS) tumors (hazard ratio 0.686: 95% confidence interval: 0.479-1.162, P = 0.040). In addition, the BRAF(V600E) mutation was a poor prognostic factor in tumors with MSI-L/MSS (P = 0.020). KRAS mutations were not prognostic factors, but sub-group analysis demonstrated that mutations in KRAS codon 12 were associated with significantly worse survival than wild-type KRAS, mutations in KRAS codon 13, or mutations elsewhere. MSI and the BRAF(V600E) mutation have a prognostic impact in colon cancer. Variable KRAS mutations may have different effects on colon cancers; further studies are needed to verify these results.