Purpose: The polycomb group protein Enhancer of Zeste Homolg 2 (EZH2), a repressor of gene transcription, has been linked to the progression of various malignancies. This study was done to examine a potential correlation of EZH2 mRNA expression with clinicopathological parameters and outcome in patients with urothelial carcinoma (UC) of the bladder.
Methods: We determined the relative EZH2 gene expression by quantitative RT-PCR in tumor specimens from a cohort of 100 patients with UC (mean follow-up 44.2 months). EZH2 expression levels were correlated to pathological tumor features and outcome.
Results: Enhancer of Zeste Homolg 2 was expressed in 90% of the tumor samples. Expression levels increased in parallel with tumor stage (P = 0.002). High grade UC displayed significantly elevated EZH2 levels compared to low grade disease (P < 0.0001). High EZH2 expression was related to an abbreviated time to recurrence in muscle invasive carcinomas (pT >/= 2) (P = 0.028). No such correlation was detected in the group of superficial tumors (pT </= 1) (P = 0.191). High EZH2 expression levels were associated with an increased risk of tumor related death in the univariate analysis (relative risk, 3.1; P = 0.029). This association became non-significant when the prognostic effect of tumor stage was considered in a multivariate model.
Conclusions: Enhancer of Zeste Homolg 2 expression is related to an aggressive tumor behavior but due to its strong association with pathological features, EZH2 levels do not provide independent prognostic information.