Role of fibroblast growth factor receptors in esophageal squamous cell carcinoma

We previously reported that the expression of fibroblast growth factor receptor-like 1 (FGFRL1) was associated with the progression of esophageal squamous cell carcinoma (ESCC). However, the clinical roles of FGFR1, FGFR2, FGFR3, and FGFR4 in ESCC have not yet been examined in detail. Furthermore, it currently remains unclear why FGFRL1 is a prognostic factor for ESCC. A squamous cell carcinoma tissue microarray established in Toyama University was used to evaluate the expression of the 4 FGFRs. Sixty-nine ESCC specimens were obtained from patients who had undergone surgery between 1990 and 2008. The immunohistochemical results obtained herein were compared to those for FGFRL1 from our previous study. We also determined whether FGFRL1 bound to other FGFRs that were selected using the tissue microarray analysis. The frequency of different FGFR overexpression combinations revealed that FGFRL1, FGFR1, and FGFR4 were the predominant types. In contrast to FGFRL1, no association was observed between the expression of each FGFR and patient prognosis. Regarding the combination analysis, 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. The results of the proximity ligation assay demonstrated that FGFRL1 bound to FGFR1 and FGFR4. Of the 5 FGFRs examined, the expression of FGFRL1 was the main prognostic factor in ESCC patients. FGFR1 and FGFR4 may be sub-driving factors of ESCC as well as the main targets of the heterodimer of FGFRL1.