Abstract: Background and purpose: Alterations in fibroblast growth factor receptor 3 (FGFR3) and phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA) have been implicated in the pathogenesis of various carcinomas. However, clinicopathological significances have not been clearly established. The aim of our study was to investigate the mutation of FGFR3 and PIK3CA to analyze the prognostic and predictive significance in bladder cancer. Methods: Study cohorts included 63 cases of bladder carcinoma who received surgical treatment in the Zhangjiagang TCM Hospital Affiliated toNanjing University of Chinese Medicine. The mutation status and overexpression of FGFR3 and PIK3CA were investigated. The findings were analyzed for the association with relevant clinicopathological findings. Kaplan-Meier method was used in survival analysis. Multivariate COX model was used to analyze the factors that might affect the prognosis of bladder carcinoma. Results: Of 63 patients, FGFR3 mutations were found in 11 patients (17.46%), and FGFR3 protein overexpression was observed in 21 patients (33.33%); PIK3CA mutations were found in 5 patients (7.93%), and 35 patients had overexpression of PIK3CA protein (55.56%). FGFR3 mutations were correlated with a pattern of different age and recurrence, while PIK3CA mutation was not associated with the relevant clinicopathological parameters. There were 2 PIK3CA ^mut in 11 cases of FGFR3 ^mut and 3 PIK3CA ^mut in 52 cases of FGFR3 ^wt (P<0.05). Kaplan-Meier survival analysis showed there was no significant difference in overall survival (OS) and progression-free survival (PFS) between patients with and without PIK3CA mutations. FGFR3 mutations were significantly correlated with shorter PFS, but had no significant influence on OS. Multivariate COX proportional hazards model analysis of OS and PFS showed FGFR3 and PIK3CA mutations were not independent predictors of OS, whereas FGFR3 mutations and smoking were independent predictors of PFS. Conclusion: FGFR3 mutation is an adverse prognostic factor. PIK3CA mutation is more frequent in bladder neoplasm with FGFR3 mutation, which contributes to the malignant behavior of FGFR3 mutant bladder neoplasm.

Key words: Fibroblast growth factor receptor 3, Phosphoinositide 3 kinase catalytic alpha polypeptide, Gene mutation, Bladder carcinoma, Prognosis