BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy

J Surg Oncol. 2012 Aug 1;106(2):123-9. doi: 10.1002/jso.23063. Epub 2012 Feb 13.

Abstract

Background and objectives: In metastatic colorectal cancer, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti-epidermal growth factor receptor (EGFR) treatment and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver metastases specimens on overall survival (OS) in patients following colorectal liver metastasectomy.

Methods: Liver metastases specimens (n = 292) obtained from patients after liver metastasectomy were used to determine the KRAS/BRAF genotype. Associations between clinicopathological parameters and KRAS/BRAF genotype were identified by univariate and multivariate analyses using the Cox proportional hazards model. The impact of KRAS/BRAF genotype on survival was analyzed using the Kaplan-Meier method.

Results: The 5-year survival rate of the cohort was 55.8%. The KRAS and BRAF mutation rates were 38.0 and 2.1%, respectively. BRAF genotype, but not KRAS, was found to be an independent prognostic biomarker (HR = 5.181, P = 0.002) after adjustment for other significant confounding clinicopathological variates: Number of liver metastases (HR = 1.983, P = 0.009), concomitant extrahepatic disease (HR = 1.858, P = 0.014), and surgical margin (HR = 3.241, P < 0.001). BRAF genotype was an independent prognostic biomarker in patients with liver metastases only after metastasectomy (HR = 6.245, P < 0.003).

Conclusions: BRAF mutation is an independent prognostic biomarker for colorectal liver metastasectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery*
  • Male
  • Metastasectomy*
  • Middle Aged
  • Mutation*
  • Odds Ratio
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins