Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability (MSI) status in Japanese colorectal cancer (CRC) population. METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage I-III CRC and examined associations of these mutations with disease-free survival (DFS) and overall survival (OS) using uni- and multivariate Cox proportional hazards models. RESULTS: KRAS and BRAF mutations were detected in 312 (38%) of 812 and 40 (5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males (P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender (P = 0.006), proximal tumor location (P < 0.001), mucinous or poorly differentiated histology (P < 0.001), and MSI-high tumors (P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS (HR = 1.35; 95%CI: 1.03-1.75) and OS (HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS (HR = 2.20; 95%CI: 1.19-4.06) and OS (HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS. CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected CRC.