Abstract 568: Fibroblast growth factor receptors 2 is a novel therapeutic target in esophagogastric junction adenocarcinoma

Abstract Background: The prognosis of esophagogastric junction (EGJ) adenocarcinoma remains poor, though it is increasing worldwide. The fibroblast growth factor receptors (FGFRs) play critical roles in various human cancers, especially FGFR2 amplification has been implicated as a key genetic alteration in EGJ adenocarcinoma. In this study, we confirmed that FGFR2 can be a therapeutic target for EGJ adenocarcinoma. Methods: Utilizing 200 cases with EGJ adenocarcinoma (Siewert types I-III), FGFR2 copy number was assayed by Real-time PCR (using RNaseP as a referent), and FGFR2 expression was detected by immunohistochemistry. We examined whether FGFR2 amplification correlates with FGFR2 expression. The associations between FGFR2 expression and clinicopathological factors, and prognostic impact of FGFR2 expression were examined. We investigated the role of FGFR2 in cell proliferation, invasion, apoptosis and cell cycle, using OACM 5.1C (FGFR2 overexpressing cell line), by siRNA technique targeting FGFR2. Results: FGFR2 amplification was detected in 33 (22%) cases, and FGFR2 expression was observed in 112 (58%) cases. FGFR2 amplification significantly correlated with FGFR2 expression (p = 0.045). FGFR2 expression was significantly associated with tumor depth of invasion, nodal involvement, distant metastasis, lymphatic invasion, and vascular invasion (all, p < 0.001). In survival analysis, tumors harboring FGFR2 expression experienced significantly unfavorable outcome (p = 0.039). We observed that si-FGFR2 significantly suppressed phosphorylation of Akt and Erk, resulting in suppressing cell proliferation and invasion; and inducing apoptosis and cell-cycle arrest (p<0.001). We also confirmed that FGF 7 promoted the proliferation and AZD4547 inhibited the proliferation through RAS-ERK and PI3K-AKT pathways. Conclusion: FGFR2 can be a therapeutic target for EGJ adenocarcinoma. Citation Format: Ryuma Tokunaga, Yu Imamura, Kenichi Nakamura, Takatsugu Ishimoto, Shiro Iwagami, Junji Kurashige, Daisuke Izumi, Keisuke Kosumi,, Takaaki Higashi, Katsunobu Taki, Yukiharu Hiyoshi, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Saeki Hiroshi, Eiji Oki, Yoshihiko Maehara, Hideo Baba. Fibroblast growth factor receptors 2 is a novel therapeutic target in esophagogastric junction adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 568. doi:10.1158/1538-7445.AM2015-568