Expression Profile of the Polycomb Group Protein Enhancer of Zeste Homologue 2 and its Prognostic Relevance in Renal Cell Carcinoma

Purpose: EZH2 increases the proliferation rate and apoptosis resistance of renal cell carcinoma cell lines. To date its clinical impact on the outcome in patients with renal cell carcinoma is not known. To our knowledge this is the first study of the association of EZH2 expression with histopathological features and disease outcomes in a large cohort of patients who underwent surgery for renal cell carcinoma. Materials and Methods: Real-time reverse transcriptase-polymerase chain reaction was done to quantify EZH2 expression in malignant and adjacent benign renal tissue from a cohort of 119 patients with clear cell renal cell carcinoma. Median followup was 51 months. Immunohistochemistry was performed in a subset of samples. The impact of EZH2 expression on clinicopathological tumor features and outcome was investigated. Results: EZH2 was over expressed in renal cell carcinoma compared to adjacent benign renal parenchyma (median 57.02, range 0 to 368.11 vs 0, range 0 to 280.87, p < 0.001). Immunohistochemistry showed concordant results and revealed EZH2 protein predominantly located in the nucleus. EZH2 expression was not associated with histopathological tumor features and patient characteristics. High EZH2 levels predicted a lower disease recurrence rate on univariate and multivariate analysis (p = 0.047 and 0.037, respectively). Conclusions: These data support a role of EZH2 expression for renal cell carcinoma tumorigenesis rather than tumor progression. Contrary to previous EZH2 findings in cases of various human malignancies, high tumor EZH2 levels appear to indicate less aggressive tumor phenotypes with a favorable prognosis in renal cell carcinoma cases. Our findings suggest that EZH2 provides not only a potential therapeutic target, but also a molecular parameter for outcome prediction in patients with renal cell carcinoma.