Tissue Expression of Erythropoietin Predicts Survival Rates in Clear Cell Renal Cell Carcinoma

OBJECTIVE: To evaluate immunohistochemical erythropoietin (EPO) expression in clear cell renal cell carcinoma (ccRCC), its association with major clinicopathological variables and its prognostic impact. METHODS: A total of 220 patients with renal cell carcinoma (RCC) surgically treated between 1989 and 2009 were evaluated in this multi-institutional study. All the cases were reviewed by a single pathologist and the immunohistochemical reactivity to EPO was analysed using tissue microarray. RESULTS: A total of 176 patients with ccRCC were considered, with an average of 48 months of follow-up. Of the tumours evaluated, 47 (26.7%) were negative for EPO expression, and 129 (73.3%) were positive. EPO expression was associated with incidental tumour (p = 0.016), tumour size (p = 0.015), Karnofsky Performance Score (KPS) (p = 0.016), blood transfusion (p = 0.009) and adrenal involvement (p = 0.038). The median ages of the patients with positive and negative EPO expression were 56.2 years and 66.6 years. Immunohistochemical EPO expression affected overall survival (OS) and disease-specific survival (DSS) rates. The DSS rates of the patients whose tissue was positive and negative for EPO expression were 85.3% and 76.1%, respectively (p = 0.044). In a multivariate analysis, the absence of EPO expression proved to be a bad prognostic factor and negatively affected the OS (p < 0.001) and DSS (p < 0.001) rates. CONCLUSION: The absence of tumour EPO expression is an independent predictive factor with a negative effect on survival rates. The use of EPO as possible marker in the management of ccRCC patients requires further studies and a better understanding of the role of EPO in tumour biology.