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. 2010 Oct 4:10:524.
doi: 10.1186/1471-2407-10-524.

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

Nina Wagener  1 , Stephan Macher-Goeppinger, Maria Pritsch, Johannes Hüsing, Karin Hoppe-Seyler, Peter Schirmacher, Jesco Pfitzenmaier, Axel Haferkamp, Felix Hoppe-Seyler, Markus Hohenfellner
Affiliations

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

Nina Wagener et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
EZH2 protein expression in renal cell carcinoma (RCC) and corresponding normal tissue. A Negative control: RCC tissue specimen (clear cell carcinoma), the anti-EZH2 antibody was omitted. B Normal adult kidney tissue, adjacent to the RCC tumor tissue shown in C. C Overview (left panel) and higher resolution (right panel) of the boxed area of an RCC sample (clear cell carcinoma), showing very high (> 50%) nuclear EZH2 expression (arrows). D Overview (left panel) and higher resolution (right panel) of an RCC sample (clear cell carcinoma) showing >5-25% nuclear EZH2 expression (arrows). E Overview (left panel) and higher resolution of an RCC sample (clear cell carcinoma) exhibiting 0% nuclear EZH2 staining. Scale bars, 5 μm.
Figure 2
Figure 2
Kaplan Meier survival curves of cancer specific survival (CSS). A CSS rates of RCC patients with non-metastatic and metastatic disease. B CSS rates in non-metastasized RCC. C CSS rates in metastatic RCC.
See this image and copyright information in PMC

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