27 Background: Previous studies showed that gene mutations of KRAS, NRAS, BRAF, and PIK3CA are associated with a poor prognosis or resistance of anti-EGFR antibody in metastatic colorectal cancer. On the other hand, the frequency and clinical significance of these gene mutations have not been clarified in metastatic gastric cancer (mGC). Methods: We gathered formalin-fixed paraffin-embedded tumor samples from 168 patients who were diagnosed gastric cancer and underwent gastrectomy between September 1995 and March 2008. Among 168 patients, we selected the mGC patients who received systemic chemotherapy. We retrospectively evaluated the mutation status of KRAS (exon2, 3, 4), NRAS (exon 2, 3), BRAF (exon 15) and PIK3CA (exon 9, 20) and prognosis in patients who received chemotherapy by gene mutation status. Results: A total 125 of patients were included in this analysis. Regimens of first line chemotherapy were 5-FU (24.0%), CPT-11/CDDP (31.2%), S-1 (33.6%), 5-FU/MTX (8.0%) and others (3.2%). Mutations of KRAS codon 12/13 (6.4%), PIK3CA exon9 (4%), PIK3CA exon20 (0.8%), and NRAS codon 12/13 (2.4%) were detected by direct-sequence method. Mutations of KRAS codon 61, KRAS codon 146, BRAF V600E and NRAS codon 61 were not detected. There were no significant differences in overall survival (OS) by mutation status of KRAS and PIK3CA. Patients with NRAS codon 12/13 mutation had poor prognosis (MSTF15.5 vs 9.4 months, adjusted HR: 5.327(95%CI: 1.566-18.096)). Conclusions: Mutations in KRAS codon 61, KRAS codon 146, BRAF V600E, NRAS codon 61 were not detected, and frequency of mutation in PIK3CA exon 9, PIK3CA exon 20 and NRAS codon 61 were rare in mGC. Although our study has several limitations, mutation in NRAS codon 12/13 may be a poor prognostic factor in mGC who received systemic chemotherapy and further accumulation of cases are needed.
Novel Agents in Heavily Pretreated Metastatic Gastric Cancer: More Shadows Than Lights
