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

BMC Cancer

Research Article

Johannes Hüsing¹  Maria Pritsch²  Jesco Pfitzenmaier³  Axel Haferkamp⁴  Markus Hohenfellner⁵  Karin Hoppe-Seyler⁶  Felix Hoppe-Seyler⁶  Nina Wagener⁷  Peter Schirmacher⁸  Stephan Macher-Goeppinger⁸ 

[1] Coordination Centre for Clinical Trials (KKS), University of Heidelberg, Voßstraße 2, 69115, Heidelberg, Germany;Department of Medical Biometry, University of Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany;Department of Urology, Evangelisches Krankenhaus Bielefeld, Schildescher Strasse 99, Bielefeld, 33611, Germany;Department of Urology, University of Frankfurt am Main, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany;Department of Urology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany;German Cancer Research Center, Molecular Therapy of Virus-Associated Cancers (F065), Im Neuenheimer Feld 242, 69120, Heidelberg, Germany;German Cancer Research Center, Molecular Therapy of Virus-Associated Cancers (F065), Im Neuenheimer Feld 242, 69120, Heidelberg, Germany;Department of Urology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany;Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany;

关键词: Renal Cell Carcinoma;    Cancer Specific Survival;    Renal Cell Carcinoma Patient;    Renal Cell Carcinoma Cell Line;    Concordance Probability;   

DOI  :  10.1186/1471-2407-10-524

 received in 2010-04-01, accepted in 2010-10-04,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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).MethodsEZH2 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.ResultsDuring 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).ConclusionsThis study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.

【 授权许可】

Unknown   
© Wagener et al; licensee BioMed Central Ltd. 2010. This article is published under license to 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.