Background: The fibroblast growth factor receptor (FGFR) tyrosine kinase family, which is comprised of four kinases that differentially respond to 18 FGF ligands, has long been implicated in cancer. Among them, activating somatic mutations in FGFR2 have been recently identified in several types of human cancer and are shown to be sensitive to FGFR2 kinase inhibition in the cell lines bearing such FGFR2 mutations, implicating FGFR2 as a novel therapeutic target. Therefore, we undertook this study to understand the clinical impact of FGFR2 amplification on gastric cancer patients. Patients and Methods: FGFR2 amplification was tested by qPCR using TaqMan probe and dual-color FISH in a panel of 37 gastric cancer cell lines and tumor specimens from 482 gastric cancer patients. Results: Of the 482 patients, 119 (24.8%) of the patients had FGFR2 copy number greater than 3.0 copies. FGFR2 amplification was not associated with clinicopathological parameters such as age, sex, histology, Bormann type, Lauren Classification, tumor location and TNM staging. Patients with FGFR2 amplification showed a trend toward shorter DFS (5-year DFS; 49.6% vs. 59.6%; FGFR2 amplification (+) vs. FGFR2 amplification (-); P=.065) and poorer survival (5-year OS; 47.9% vs. 58.41%; P=.084). We are currently performing preclinical study to investigate FGFR2-correlated sensitivity to several types of molecular-targeted agents. Conclusion: These results suggest that the FGFR2 amplification plays an important role in determining prognosis in gastric cancer patients. However, this study did not cover a predictive role of the FGFR2 amplification for the treatment response to FGFR2 kinase inhibitors, which should be further explored as a novel therapeutic target in upcoming clinical trials.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 660.