Background: Clear cell renal cell carcinoma (CCRCC) represents the most common malignant adult renal tumor. Its poor prognosis is due to poor response to current treatment options. Identification of new therapeutic targets is a priority. Enhancer of zeste homolog 2 (EZH2) expression is associated with aggressive behavior in different cancers. Vascular endothelial growth factor (VEGF) is strong angiogenic agent that promotes angiogenesis during the growth of tumor. Aim: To assess the significance of immunohistochemical expression of EZ2H and VEGF on tumor behavior, prognosis and patient survival in clear cell renal cell carcinoma. Methods: Immunohistochemical expressions of EZH2, VEGF,Ki-67were evaluated in 25 cases of CCRCC, correlated with each other , with clinicopathological parameters and patients survival. Results: Expression of EZH2 was significantly correlated with tumor grade and stage (p< 0.001), metastasis to lymph node (p=0.016), Ki67 expression (p= 0.014) and with local recurrence of the tumor (p= 0.001) in CCRCC cases. Vascular Endothelial Growth Factor was significantly positively correlated with tumor grade and stage (p< 0.001), Ki67 expression (p= 0.008) and local recurrence of the tumor (p= 0.001) while no correlation was found with lymph node metastasis (p=0.096). Direct correlation was detected between EZH2 and VEGF expression (p< 0.001), and a significant positive correlation was detected between ki-67 and both EZH2 (p= 0.003), and VEGF (p<0.001).High EZH2 and VEGF expression was significantly positively correlated with worse 2-year overall survival (OS) (p < 0.001 and p= 0.009, respectively).Conclusion: EZH2 and VEGF can be considered as independent prognostic markers in CRCC and may be used as a target for therapy in these cases.

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