Incidence and prognostic impact of KRAS and BRAF mutations in patients undergoing liver surgery for colorectal metastases.

3616 Background: Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer metastases, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the prevalence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). Methods: KRAS and BRAF analysis was performed on 202 patients undergoing curative intent surgical therapy of CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS: codon 12/13, BRAF: V600E). The frequency of mutations was ascertained and their impact on outcome determined relative to other clinicopathologic factors. Results: KRAS gene mutations were detected in 58/202 patients (29%) undergoing surgery for CRLM, comparable to that reported in non-surgical patient series. In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2%) patients. KRAS mutations were associated with worse long-term survival (HR=2.13, CI=1.25-3.65), as well as risk of recurrence (HR=1.89, CI=1.12-3.19). ). In addition, KRAS mutation was also associated with risk of recurrence following surgical therapy (HR=1.89, CI=1.12-3.19).While other clinicopathologic features, including tumor number, CEA and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited the ability to determine its prognostic impact. Conclusions: While KRAS mutations were found in approximately one third of patients, BRAF mutations were found in only 2% of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and disease-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.