Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma.

Overexpression of EZH2 and inactivation or loss of PTEN expression was observed in invasive and metastatic tumors. However, their expressions and clinical significances in gallbladder cancer (GBC) have rarely been reported. In this study, we investigated EZH2 and PTEN expression in an extensive collection of human gallbladder cancer samples and benign lesions of gallbladder using immunohistochemistry. Overexpression of EZH2 was detected in 53.7% of gallbladder adenocarcinomas associated with poor differentiation, lymph node metastasis, and invasion, while loss of PTEN expression was identified in 51.8% of adenocarcinomas with high grade, metastatic, and invasive tumors. Univariate Kaplan-Meier analysis showed that overexpression of EZH2 (p=0.013) and loss of PTEN expression (p=0.008) were significantly associated with decreased overall survival. Multivariate Cox regression analysis revealed that overexpression of EZH2 (p=0.011) or loss of PTEN expression (p=0.009) is a predictor of poor prognosis in gallbladder adenocarcinoma. Our study suggests that overexpression of EZH2 and loss of PTEN expression might be closely related to the carcinogenesis, progression, clinical biological behavior, and prognosis of gallbladder adenocarcinoma.