AUTHOR=Yang Qiwei , Huo Sibo , Sui Yujie , Du Zhenwu , Zhao Haiyue , Liu Yu , Li Wei , Wan Xin , Liu Tongjun , Zhang Guizhen 

TITLE=Mutation Status and Immunohistochemical Correlation of KRAS, NRAS, and BRAF in 260 Chinese Colorectal and Gastric Cancers

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00487

DOI=10.3389/fonc.2018.00487

ISSN=2234-943X

ABSTRACT=<p><italic>KRAS, NRAS</italic> and <italic>BRAF</italic> are kinases involved in the RAS-RAF-MAPK signaling pathway and also potential tumor-driven genes. Patients with <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> mutations are resistant to anti-<italic>EGFR</italic> monoclonal antibody therapy. The main purpose of this study is to investigate the mutation status and distribution of <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> in Chinese colorectal and gastric cancers, and to explore the histopathological changes and related immunohistochemical marker changes caused by these mutations. The mutation status of <italic>KRAS</italic> (exons 2, codon 12/13), <italic>NRAS</italic> (exons 2/3/4, codon 12/13/59/61/117/146) and <italic>BRAF</italic> (exons 15, codon 600) were detected by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in 86 colon cancer, 140 rectal cancer and 34 gastric cancer tissues. Then, the frequencies and distribution of <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> mutations were described in detail. Furthermore, the relationship between <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> mutations and the features of histopathological and related immunohistochemical markers were analyzed. The results showed that <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> mutation rates in colon cancer were 44.2, 1.2, and 3.5%; in rectal cancer were 37.1, 4.3, and 0.7%; in gastric cancer were none, none and 2.9%. The mutation rate of <italic>KRAS</italic> in female (48.8%) is significantly higher than that of male (27.8%), and the mutation rate increased with the higher degree of differentiation. Additionally, the mutation rate of <italic>BRAF</italic> detected by ARMS-PCR (1.77%) was significantly lower than that by immunohistochemistry (4.11%). It also showed that the <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> mutation status had a certain relationship with the expression of some immunohistochemical markers. This study provides more data support for clinical research on <italic>KRAS</italic>/<italic>NRAS</italic>/<italic>BRAF</italic> mutation in CRCs or gastric cancers.</p>