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

  • Original Article – Clinical Oncology
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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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Acknowledgments

We are grateful to Y. Kubota and T. Shishino for their technical assistance (Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan). This study was supported by a grant from the Ministry of Education, Culture Sports, Science and Technology of Japan (M. Kakenhi; Grant Number 15H05792).

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

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

  2. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yu Nakaji & Yoshinao Oda

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  1. Yu Nakaji
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  2. Eiji Oki
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  10. Yoshihiko Maehara
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Correspondence to Eiji Oki.

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All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the Institutional and National Research Committees and with the 1964 Helsinki Declaration and its later amendments.

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Nakaji, Y., Oki, E., Nakanishi, R. et al. Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer. J Cancer Res Clin Oncol 143, 151–160 (2017). https://doi.org/10.1007/s00432-016-2275-4

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  • DOI: https://doi.org/10.1007/s00432-016-2275-4

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