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

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• 作者：Nina Wagener (1) (2)
  Stephan Macher-Goeppinger (3)
  Maria Pritsch (4)
  Johannes Hüsing (5)
  Karin Hoppe-Seyler (1)
  Peter Schirmacher (3)
  Jesco Pfitzenmaier (6)
  Axel Haferkamp (7)
  Felix Hoppe-Seyler (1)
  Markus Hohenfellner (2)
  
• 刊名：BMC Cancer
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：10
• 期：1
• 全文大小：1265KB
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  41. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/524/prepub
  
• 作者单位：Nina Wagener (1) (2)
  Stephan Macher-Goeppinger (3)
  Maria Pritsch (4)
  Johannes Hüsing (5)
  Karin Hoppe-Seyler (1)
  Peter Schirmacher (3)
  Jesco Pfitzenmaier (6)
  Axel Haferkamp (7)
  Felix Hoppe-Seyler (1)
  Markus Hohenfellner (2)
  
  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, m Neuenheimer Feld 305, 69120, Heidelberg, Germany
  5. Coordination Centre for Clinical Trials (KKS), University of Heidelberg, Vo?stra?e 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
  
• ISSN：1471-2407

文摘

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.