Prognostic impact of KRAS mutant type and MET amplification in metastatic and recurrent gastric cancer patients treated with first-line S-1 plus cisplatin chemotherapy
Satoshi Matsusaka1, Takashi Kobunai2, Noriko Yamamoto3, Keisho Chin1, Mariko Ogura1, Gotaro Tanaka4, Kazuaki Matsuoka2, Yuichi Ishikawa3, Nobuyuki Mizunuma1 and Toshiharu Yamaguchi5
1 Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
2 Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokyo, Japan
3 Department of Pathology, Japanese Foundation for Cancer Research, Tokyo, Japan
4 Applied Pharmacology Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan
5 Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
Correspondence:
Satoshi Matsusaka, email:
Keywords: gastric cancer, KRAS, MET, DNA copy number, immunohistochemistry
Received: January 14, 2016 Accepted: February 06, 2016 Published: February 16, 2016
Abstract
Receptor tyrosine kinase (RTK)-related genes, including HER2, EGFR, MET, FGFR2 and KRAS, are target molecules that are clinically beneficial in gastric cancer (GC). We investigated the correlation between RTK-related genes and the curative effect of first-line S-1 plus cisplatin (SP) combination chemotherapy in metastatic and recurrent GC. We enrolled 150 patients with histopathologically confirmed metastatic and recurrent GC treated with SP. KRAS mutation was detected using direct sequencing. DNA copy number was measured by real-time PCR. Formalin-fixed paraffin-embedded specimens were examined immunohistochemically for HER2, EGFR, FGFR2 and MET. Among 144 patients, KRAS mutation was detected in five (3.5%) at codon 12 and one (0.7%) at codon 13. FGFR2, EGFR, HER2, MET and KRAS gene amplification was suggested in 4.4%, 5.9%, 9%, 3.7% and 10.3% of patients, respectively. KRAS mutation, but not KRAS amplification, was associated with significantly shorter overall and progression-free survival. MET membranous overexpression was associated with a significantly higher tumor response. MET amplification was associated with significantly shorter overall survival. We show for the first time that KRAS mutation and MET amplification are promising predictive markers in metastatic and recurrent GC patients treated with SP. KRAS status may be a useful prognostic marker in patients treated with SP.
