Abstract 3556: Fibroblast growth factor receptor 2 is associated with poor overall survival in clear cell carcinoma of the ovary and may be a novel therapeutic approach
Authors: Itamochi Hiroaki , Oumi Nao , Oishi Tetsuro , Taniguchi Fuminori , Shoji Tadahiro , Fujiwara Hiroyuki , Sugiyama Toru , Suzuki Mitsuaki , Kigawa Junzo , Harada Tasuku 
Published: August 2015

Objective: Clear cell carcinoma of the ovary (CCC) has a poor prognosis because of its resistance to conventional platinum- or taxane-based chemotherapy. We previously found that both gene and protein expression of fibroblast growth factor receptor (FGFR) 2 are increased in CCC. FGFR activate intracellular signaling pathways that are known to regulate key biological processes. Overexpression of FGFR2 has been reported in several cancers such as lung, pancreatic, breast and colorectal cancers, and has been associated with a poor prognosis. We therefore investigated whether FGFR2 could be a biomarker and a therapeutic target for CCC.

Methods: We analyzed the protein expression of FGFR2 by immunohistochemical staining in paraffin-embedded tumors from 112 CCC patients, and evaluated the association of this molecular parameter with clinical outcome. Next, we examined the expression of proteins of the FGFR2 signaling pathway in 12 ovarian cancer cell lines (11 CCC and one serous adenocarcinoma) by western blotting. The sensitivity of the cells to a FGFR inhibitor was determined by WST-8 assay, and cell cycle distribution was assessed by flow cytometry.

Results: One hundred and eight of 112 (96%) CCC tumors showed positive expression of FGFR2. No significant associations between the levels of FGFR2 expression and patient age or disease stage were found. The 5-year survival rate of patients with moderate or strong tumor expression of FGFR2 was significantly lower than those with an absent or low tumor expression of FGFR2 (54% vs. 79%). Multivariable analysis revealed that FGFR2 expression and disease stage were independent prognostic factors. All 11 CCC cell lines expressed substantial amounts of FGFR2 protein compared with the serous adenocarcinoma cell line. The protein expression level of 8 of 11 CCC cell lines was more than five times that of the serous adenocarcinoma cell line, and thus we defined these CCC cell lines as high FGFR2-expressing cells. The FGFR inhibitor effectively suppressed the growth of high FGFR2-expressing CCC cells compared with low FGFR2-expressing cells, with induction of G1 cell cycle arrest and downregulation of phosphorylated (p-) Akt and p-ERK expression.

Conclusions: The FGFR2 protein may be a promising biomarker that is predictive of patient outcome, and FGFR2 is a potential therapeutic target for CCC. Further study of FGFR inhibitor in the treatment of CCC is warranted.

Citation Format: Hiroaki Itamochi, Nao Oumi, Tetsuro Oishi, Fuminori Taniguchi, Tadahiro Shoji, Hiroyuki Fujiwara, Toru Sugiyama, Mitsuaki Suzuki, Junzo Kigawa, Tasuku Harada. Fibroblast growth factor receptor 2 is associated with poor overall survival in clear cell carcinoma of the ovary and may be a novel therapeutic approach. [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 3556. doi:10.1158/1538-7445.AM2015-3556