Abstract 3447: Role of fibroblast growth factor receptors in esophageal squamous cell carcinoma

Abstract

Abstract Introduction: MicroRNA-210 regulates cancer cell proliferation by targeting fibroblast growth factor receptor-like 1 (FGFRL1) in esophageal squamous cell cancer (ESCC) (JBC 2011). The expression of FGFRL1 has been associated with tumor growth and lymph node metastasis. In the present study, we analyzed and compared the expression of FGFR1, FGFR2, FGFR3, and FGFR4 with that of FGFRL1 using a tissue microarray. We also examined whether antibodies for FGFRL1 inhibited the growth and motility of ESCC cells. Material and Methods: A squamous cell carcinoma tissue microarray established in Toyama University was used to evaluate the expression of the 5 FGFRs. Sixty-nine specimens of ESCC were obtained from 62 male and 7 female patients, with an average age of 64.4 years old, that underwent surgery between 1990 and 2008. The TNM stages of these patients were as follows; stage 1: 7, stage 2a; 10, stage 2b; 10, stage 3; 35, stage 4; 7. The immunohistochemical results of these patients were scored according to intensity and distribution after a careful examination by two independent researchers. The ESCC cell line KYSE520 was used for experimental analyses. Polyclonal and monoclonal antibodies for FGFRL1 were used to evaluate the function of FGFRL1. Results: The percentage of patients who tested positive for the expression of the different FGFRs was as follows: FGFRL-1, 81% (56/69); FGFR1, 65% (37/57); FGFR2, 36% (22/61); FGFR3, 21% (12/57); FGFR4, 39% (22/56). The prognosis of FGFRL1 positive patients was significantly worse than that of FGFRL1 negative patients. (P=0.0311). Both polyclonal and monoclonal antibodies inhibited the growth (50% reduction) and motility (25% reduction) of ESCC cells. However, no association was observed between the expression of the other FGFRs and patient prognosis. Regarding combination analysis of the expression of each FGFR, patients that co-expressed FGFRL1 and FGFR1 had the worst prognosis, while patients who tested negative for the expression of both FGFRL1 and FGFR4 had the best prognosis. Conclusions: Among the 5 FGFRs, the expression of FGFRL1 was the main oncogenic driving factor in ESCC patients. The expression of FGFR1 and FGFR4 may be a sub-driving factor of ESCC. Citation Format: Yutaka Shimada, Tomoyuki Okumura, Takuya Nagata, Yoshinori Takei, Kazuhiro Tsukada, Kazuharu Shimizu. Role of fibroblast growth factor receptors in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3447. doi:10.1158/1538-7445.AM2014-3447