title: BRAF mutation may have different prognostic implications in early- and late-stage colorectal cancer.
abstract: The prognostic implication of BRAF mutant colorectal cancer remains paradoxical. Records of BRAF mutant and wild-type colorectal cancer patients at all stages were reviewed. Clinicopathologic features, including microsatellite instability, CpG islands methylator phenotype, and overall survival, of these patients were analyzed. Between 2005 and 2013, 428 colorectal cancer patients were enrolled in this study. The overall survival between BRAF mutant and wild-type patients with early-stage (stages I and II) colorectal cancer differed nonsignificantly (P = 0.99). By contrast, in late-stage (stages III and IV) patients, the median overall survival of BRAF mutant patients (N = 25) was significantly poorer than that of BRAF wild-type (N = 207) patients (BRAF mutant: 21.3 months (95% confidence interval [CI] 7.1-35.5); BRAF wild-type: 53.5 months (95% CI 37.5-69.5), P < 0.0001). In early-stage patients, we found that BRAF mutation was significantly associated with CpG island methylator phenotype-positive (P < 0.001), and microsatellite instability-high status (P = 0.0013). Conversely, in late-stage patients, BRAF mutation was significantly associated with CpG island methylator phenotype-positive (P = 0.0015) and the right-side colon (P = 0.014). BRAF mutation may have different prognostic implications in early- and late-stage colorectal cancer.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10002, Taiwan.|National Taiwan University Cancer Center, Taipei, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10002, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jau-Yu
authors.initials: JY
authors.lastname: Liau
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jia-Huei
authors.initials: JH
authors.lastname: Tsai
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Tseng
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.affiliation: Division of Colorectal Surgery, National Taiwan University Hospital, Taipei, Taiwan.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jin-Tung
authors.initials: JT
authors.lastname: Liang
authors.affiliation: Division of Colorectal Surgery, National Taiwan University Hospital, Taipei, Taiwan.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Been-Ren
authors.initials: BR
authors.lastname: Lin
authors.affiliation: Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ji-Shiang
authors.initials: JS
authors.lastname: Hung
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.|Department and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10002, Taiwan. khyeh@ntu.edu.tw.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan. khyeh@ntu.edu.tw.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. khyeh@ntu.edu.tw.
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
authors.affiliation: Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10002, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF gene mutation; Colorectal cancers; CpG island methylator phenotype (CIMP); Microsatellite instability (MSI); Prognosis