Prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for initially resectable colorectal liver metastases.

ABSTRACT

This study aimed to explore the prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLMs) that were initially resectable. Clinicopathological and outcome data of 139 consecutive patients with SCRLMs who underwent resection between July 2003 and July 2013 was collected from our prospectively established SCRLM database. The KRAS and BRAF genotypes were evaluated in the primary cancer tissues by pyrosequencing. The prognostic value of KRAS and BRAF status was assessed by Kaplan-Meier and Cox regression analyses. KRAS and BRAF mutated in 28.8% and 7.2% of the patients with SCRLMs, respectively, but the genotypes did not significantly associate with any clinicopathologic characteristics. By Kaplan-Meier survival analysis, we found KRAS mutation was not significantly associated with short overall survival (OS) (P = 0.213), but was significantly correlated with short disease-free survival (DFS) (P = 0.041); BRAF mutation was significantly associated with both short OS and DFS (P = 0.001, P<0.001, respectively). Multivariate survival analysis showed KRAS mutation was an independent negative prognostic factor for DFS (P = 0.005) and BRAF mutation was an independent negative prognostic factor for OS and DFS (P = 0.001, P<0.001, respectively). KRAS and BRAF mutation similarly contributed to an adverse prognostic effect in patients who underwent simultaneous resection for SCRLMs that were initially resectable. These findings should suggest the use of KRAS and BRAF status in current practice as an important determinant for precision surgery for initially resectable SCRLMs.