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

To evaluate immunohistochemical erythropoietin (EPO) expression in clear cell renal cell carcinoma (ccRCC), its association with major clinicopathological variables and its prognostic impact.

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.

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.

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.