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Journal of Cancer Research and Clinical Oncology

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01-01-2017 | Original Article – Clinical Oncology

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

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

Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2017

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.

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Title: Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer
Authors: Yu Nakaji
Eiji Oki
Ryota Nakanishi
Koji Ando
Masahiko Sugiyama
Yuichiro Nakashima
Nami Yamashita
Hiroshi Saeki
Yoshinao Oda
Yoshihiko Maehara
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 1/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2275-4

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