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The prognostic role of microsatellite instability, codon‐specific KRAS , and BRAF mutations in colon cancer
Author(s) -
Lin ChunChi,
Lin JenKou,
Lin TzuChen,
Chen WeiShone,
Yang ShungHaur,
Wang HuannSheng,
Lan YuanTzu,
Jiang JengKai,
Yang MuhHwa,
Chang ShihChing
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23675
Subject(s) - kras , microsatellite instability , medicine , colorectal cancer , hazard ratio , oncology , genotyping , mutation , cancer , cancer research , confidence interval , genotype , microsatellite , biology , gene , genetics , allele
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. J. Surg. Oncol. 2014; 110:451–457 . © 2014 Wiley Periodicals, Inc.