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Combined microsatellite instability and BRAF gene status as biomarkers for adjuvant chemotherapy in stage III colorectal cancer
Author(s) -
Ooki Akira,
Akagi Kiwamu,
Yatsuoka Toshimasa,
Asayama Masako,
Hara Hiroki,
Takahashi Akemi,
Kakuta Miho,
Nishimura Yoji,
Yamaguchi Kensei
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23755
Subject(s) - microsatellite instability , medicine , colorectal cancer , oncology , stage (stratigraphy) , cancer , microsatellite , gene , allele , biology , genetics , paleontology
Background The clinical relevance of combined microsatellite instability (MSI) and BRAF status for adjuvant treatment in stage III colorectal cancer (CRC) remains elusive. Methods In 405 patients with curatively resected stage III CRC, the prognostic value of combined MSI and BRAF status was assessed in four groups, as follows: high‐levels of microsatellite instability (MSI‐H) and BRAF ‐wild type, MSI‐H and BRAF ‐mutation, microsatellite stable (MSS) and BRAF ‐wild type, and MSS and BRAF ‐mutation. Results Combined MSI and BRAF status provided significant prognostic stratification of disease‐free survival (DFS), and was independently associated with worse DFS. The MSI‐H and BRAF ‐wild type group had similar outcomes to stage II CRC patients, despite no benefit from 5‐FU monotherapy. Further, patients in the MSS and BRAF ‐wild type group with stage IIIA CRC had favorable outcomes to 5‐FU monotherapy, similar to those with stage II CRC. In contrast, 5‐FU monotherapy was insufficient among patients in the MSS and BRAF ‐wild type group with stage IIIB or IIIC CRC or patients in the MSS and BRAF ‐mutation group with stage III CRC. Conclusions The combination of MSI and BRAF status serves as both a prognostic and predictive marker and may provide much‐needed guidance during the planning of therapeutic strategies. J. Surg. Oncol. 2014; 110:982–988 . © 2014 Wiley Periodicals, Inc.