Research Report
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 21, 2014; 20(15): 4370-4376
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4370
Clinical meaning of BRAF mutation in Korean patients with advanced colorectal cancer
Bun Kim, Soo Jung Park, Jae Hee Cheon, Tae Il Kim, Won Ho Kim, Sung Pil Hong
Bun Kim, Soo Jung Park, Jae Hee Cheon, Tae Il Kim, Won Ho Kim, Sung Pil Hong, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea
Author contributions: Hong SP designed the study; Kim B acquired clinical data and performed the statistical analysis; Park SJ, Cheon JH, Kim TI and Kim WH contributed equally to this study by performing data interpretation and offering important intellectual content; Hong SP and Kim B drafted the manuscript.
Correspondence to: Sung Pil Hong, MD, PhD, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea. sphong@yuhs.ac
Telephone: +82-2-22281990 Fax: +82-2-3936884
Received: September 2, 2013
Revised: November 4, 2013
Accepted: January 8, 2014
Published online: April 21, 2014
Processing time: 226 Days and 21 Hours
Abstract

AIM: To evaluate the clinicopathological features of colorectal cancer (CRC) with a v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and its molecular interaction with microsatellite instability (MSI) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in patients with advanced CRCs.

METHODS: From October 2009 to December 2011, 141 patients with stage III (n = 51) or IV (n = 90) CRCs who were tested for the BRAF mutation at Severance Hospital were included. Among 141 patients, five were excluded due to follow-up loss. Therefore, 136 patients were included in the study. The clinicopathological data, MSI status, and KRAS/BRAF mutation status were reviewed retrospectively. In addition, to evaluating the value of BRAF mutation status, progression-free survival and overall survival in all patients were collected and compared between the BRAF wild-type group and BRAF mutation group.

RESULTS: Of 136 patients, 80 (58.8%) were male and the mean age was 59 years. BRAF and KRAS mutations were detected in 9.6% and 35.3% of patients, respectively. Only 4.3% of patients had MSI-high tumors and there were no MSI-high in tumors with a BRAF mutation. BRAF mutations tended to be more frequent in stage IV than in stage III (11.76% vs 5.88%, P = 0.370). Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without (7.69% vs 38.21%, P = 0.033). Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis (P = 0.041) and multivariate analysis (HR = 2.195; 95%CI: 1.039-4.640; P = 0.039), while progression-free survival was not different according to BRAF mutation status.

CONCLUSION: CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.

Keywords: BRAF; Colorectal cancer; Molecular features; Chemotherapy response; Prognosis

Core tip: This study identified the clinicopathological features of colorectal cancer (CRC) with BRAF mutation and its molecular interaction with microsatellite instability and KRAS targeting only to stage III/IV CRCs. These molecular markers enable the classification of CRCs into meaningful subtypes for prognosis. Our data strongly support the prognostic role of BRAF mutation in Korean patients with advanced CRC.