TY - JOUR A1 - Wagener, Nina A1 - Macher-Göppinger, Stephan A1 - Pritsch, Maria A1 - Hüsing, Johannes A1 - Hoppe-Seyler, Karin A1 - Schirmacher, Peter A1 - Pfitzenmaier, Jesco A1 - Haferkamp, Axel A1 - Hoppe-Seyler, Felix A1 - Hohenfellner, Markus T1 - Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma T2 - BMC Cancer N2 - 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. Y1 - 2010 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20074 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-81542 N1 - © 2010 Wagener et al. , licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited VL - 10 IS - 524 ER -