title: BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Teng
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Huang
authors.forename: Jen-Kou
authors.initials: JK
authors.lastname: Lin
authors.forename: Wei-Shone
authors.initials: WS
authors.lastname: Chen
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Lin
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
authors.forename: Chueh-Chuan
authors.initials: CC
authors.lastname: Yen
authors.forename: Anna Fen-Yau
authors.initials: AF
authors.lastname: Li
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chang
authors.forename: Yuan-Tzu
authors.initials: YT
authors.lastname: Lan
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Huann-Sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins