Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer

Yu Nakaji, Eiji Oki, Ryota Nakanishi, Koji Ando, Masahiko Sugiyama, Yuichiro Nakashima, Nami Yamashita, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC. Methods: In this retrospective study, tissue samples from 472 Japanese patients with CRC, stratified for MSI, were analyzed to determine the prognostic value of BRAF V600E, as assessed using IHC. Mutations in 254 patients were evaluated using the direct sequencing method to check for concordance. Results: The frequency of MSI-H was 9.3 % (44/472), and BRAF V600E mutation was detected immunohistochemically in 8.7 % patients (41/472). The sensitivity and specificity for detection of BRAF V600E mutations by IHC were 100 % (17/17) and 98.7 % (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical tumor site (P = 0.0035), histological type (P < 0.0001), and MSI status (P < 0.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio = 1.500, P = 0.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard ratio = 2.621, P = 0.0004). Conclusions: IHC using a BRAF V600E-specific antibody was useful for diagnosis and concurred with direct sequencing results. CRC cases could be stratified by combining BRAF V600E mutation and MSI status as a prognostic factor in Japanese patients.

Original languageEnglish
Pages (from-to)151-160
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume143
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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