Background: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in\r\ncolorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for\r\noverall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We\r\ninvestigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the\r\npatient population.\r\nMethods: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3\r\nclinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations\r\ndefined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site,\r\ntumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by\r\nlog rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance\r\nlevel was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical\r\nsignificance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test,\r\nwith significance level of 0.05.\r\nResults: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in\r\nsubpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole\r\npopulation. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We\r\nfound that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that\r\nKRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show\r\nevidence of heterogeneity in survival of patients with BRAF V600E mutation.\r\nConclusions: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal\r\ncancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it\r\nrepresents a marker of much higher risk than previously considered. KRAS mutation status does not seem to\r\nrepresent a strong prognostic variable
Loading....