title: BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer.
abstract: BACKGROUND
  Activating mutation of KRAS and BRAF are focused on as potential prognostic and predictive biomarkers in patients with colorectal cancer (CRC) treated with anti-EGFR therapies. This study investigated the clinicopathological features and prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC patients.
  
  
  METHODS
  Patients with advanced and recurrent CRC treated with systemic chemotherapy (n=229) were analysed for KRAS/BRAF genotypes by cycleave PCR. Prognostic factors associated with survival were identified by univariate and multivariate analyses using the Cox proportional hazards model.
  
  
  RESULTS
  KRAS and BRAF mutations were present in 34.5% and 6.5% of patients, respectively. BRAF mutated tumours were more likely to develop on the right of the colon, and to be of the poorly differentiated adenocarcinoma or mucinous carcinoma, and peritoneal metastasis. The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (40.6 months) (BRAF; HR=4.25, P<0.001, KRAS13; HR=2.03, P=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor OS (HR=4.23, P=0.019).
  
  
  CONCLUSIONS
  Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC. The KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurrent CRC.
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. tomoya.yokota@gmail.com
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: T
authors.initials: T
authors.lastname: Ura
authors.forename: N
authors.initials: N
authors.lastname: Shibata
authors.forename: D
authors.initials: D
authors.lastname: Takahari
authors.forename: K
authors.initials: K
authors.lastname: Shitara
authors.forename: M
authors.initials: M
authors.lastname: Nomura
authors.forename: C
authors.initials: C
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Mizota
authors.forename: S
authors.initials: S
authors.lastname: Utsunomiya
authors.forename: K
authors.initials: K
authors.lastname: Muro
authors.forename: Y
authors.initials: Y
authors.lastname: Yatabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf