Clinicopathological and prognostic significance of EZH2 expression in upper urinary tract carcinoma

Evidence suggests that overexpression of enhancer of zeste homologue 2 (EZH2) is associated with aggressive behavior in various cancers. However, the clinical, pathological, and prognostic associations of EZH2 expression in the upper urinary tract carcinoma have not been reported. This study aimed to investigate the significance of EZH2 expression in the upper urinary tract carcinoma by immunohistochemical analysis using a tissue microarray. High EZH2 expression was observed in 94 of 171 (55 %) cases and was significantly associated with several adverse prognostic factors, including sessile architecture, high histological grade, presence of lymphovascular invasion, concomitant carcinoma in situ, higher tumor stage, and higher Ki-67 expression (all P < 0.01). EZH2 expression status in primary and metastatic lesions was concordant in all 13 cases examined. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional hazards regression models. High EZH2 expression was significantly associated with a shorter metastasis-free survival (log-rank P = 0.005; multivariate hazard ratio, 1.85; 95 % confidence interval, 0.93-3.71) and cancer-specific survival (log-rank P = 0.006; multivariate hazard ratio, 3.08; 95 % confidence interval, 1.30-7.32) after nephroureterectomy. Our results suggest that EZH2 may serve as a novel prognostic biomarker and a potential therapeutic target in upper urinary tract carcinoma.