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Open Access Research article

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

Nina Wagener12, Stephan Macher-Goeppinger3, Maria Pritsch4, Johannes Hüsing5, Karin Hoppe-Seyler1, Peter Schirmacher3, Jesco Pfitzenmaier6, Axel Haferkamp7, Felix Hoppe-Seyler1* and Markus Hohenfellner2*

Author Affiliations

1 German Cancer Research Center, Molecular Therapy of Virus-Associated Cancers (F065), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany

2 Department of Urology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany

3 Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany

4 Department of Medical Biometry, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany

5 Coordination Centre for Clinical Trials (KKS), University of Heidelberg, Voßstraße 2, 69115 Heidelberg, Germany

6 Department of Urology, Evangelisches Krankenhaus Bielefeld, Schildescher Strasse 99, 33611 Bielefeld, Germany

7 Department of Urology, University of Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

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BMC Cancer 2010, 10:524  doi:10.1186/1471-2407-10-524

Published: 4 October 2010

Abstract

Background

The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC).

Methods

EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses.

Results

During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (> 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively).

Conclusions

This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.