BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer

被引：334
作者：
Yokota, T. [1 ,2 ]
Ura, T. [1 ]
Shibata, N. [2 ]
Takahari, D. [1 ]
Shitara, K. [1 ]
Nomura, M. [1 ]
Kondo, C. [1 ]
Mizota, A. [1 ]
Utsunomiya, S. [3 ]
Muro, K. [1 ]
Yatabe, Y. [2 ]
机构：
[1] Aichi Canc Ctr Hosp, Dept Clin Oncol, Chikusa Ku, Nagoya, Aichi 4648681, Japan
[2] Aichi Canc Ctr Hosp, Dept Pathol & Mol Diagnost, Chikusa Ku, Nagoya, Aichi 4648681, Japan
[3] Nagoya Kyoritsu Hosp, Dept Gastroenterol, Nakagawa Ku, Nagoya, Aichi 4540933, Japan
来源：
BRITISH JOURNAL OF CANCER | 2011年 / 104卷 / 05期
关键词：
BRAF; KRAS; prognostic marker; colorectal cancer; chemotherapy; ISLAND METHYLATOR PHENOTYPE; K-RAS MUTATIONS; SIGNALING PATHWAY; MISMATCH-REPAIR; STAGE-II; CETUXIMAB; COLON; KRAS; SURVIVAL; OXALIPLATIN;
D O I：
10.1038/bjc.2011.19
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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. METHOD: 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). CONCLUSION: 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. British Journal of Cancer (2011) 104, 856-862. doi:10.1038/bjc.2011.19 www.bjcancer.com Published online 1 February 2011 (C) 2011 Cancer Research UK
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页码：856 / 862
页数：7
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