title: The prognostic role of microsatellite instability, codon-specific KRAS, and BRAF mutations in colon cancer.
abstract: BACKGROUND
  This study aimed to establish a correlation between MSI, KRAS mutations, and BRAF(V600E) in colon cancer and to investigate the prognostic effect.
  
  
  METHODS
  Colon cancer patients who underwent surgical intervention were enrolled. MSI status was identified by genotyping, and the mutational statuses of KRAS and BRAF were determined by MassARRAY, targeting 22 mutations. The clinicopathological differences and correlations between these factors were analyzed.
  
  
  RESULTS
  Among 1,063 patients, tumors with MSI-H were significantly associated with BRAF(V600E) (P = 0.001). KRAS and BRAF mutations were mutually exclusive (P = 0.001). Patients with MSI-H tumors had significantly improved overall survival compared with patients that had microsatellite instability-low/stable (MSI-L/MSS) tumors (hazard ratio 0.686: 95% confidence interval: 0.479-1.162, P = 0.040). In addition, the BRAF(V600E) mutation was a poor prognostic factor in tumors with MSI-L/MSS (P = 0.020). KRAS mutations were not prognostic factors, but sub-group analysis demonstrated that mutations in KRAS codon 12 were associated with significantly worse survival than wild-type KRAS, mutations in KRAS codon 13, or mutations elsewhere.
  
  
  CONCLUSIONS
  MSI and the BRAF(V600E) mutation have a prognostic impact in colon cancer. Variable KRAS mutations may have different effects on colon cancers; further studies are needed to verify these results.
authors: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chun-Chi
authors: CC
authors: Lin
authors: Jen-Kou
authors: JK
authors: Lin
authors: Tzu-Chen
authors: TC
authors: Lin
authors: Wei-Shone
authors: WS
authors: Chen
authors: Shung-Haur
authors: SH
authors: Yang
authors: Huann-Sheng
authors: HS
authors: Wang
authors: Yuan-Tzu
authors: YT
authors: Lan
authors: Jeng-Kai
authors: JK
authors: Jiang
authors: Muh-Hwa
authors: MH
authors: Yang
authors: Shih-Ching
authors: SC
authors: Chang
mesh_terms: D000368:Aged; D003062:Codon; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; 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: D003062:Codon; 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
keywords: BRAF mutation; KRAS mutation; colon cancer; microsatellite instability; prognosis