The prognostic value of ephrin type-A2 receptor and Ki-67 in renal cell carcinoma patients: An Immunohistochemical and Bioinformatical Approach; A STROBE - compliant article

Patients with renal cell carcinoma (RCC), the most common malignant renal epithelial tumor, usually present with advanced disease and unpredicted clinical behavior. The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2) was found to be overexpressed in several malignancies and its expression was found to be associated with poor prognostic features. Our study is an observational study with the aim of investigating the prognostic value of EphA2 in RCC patients and its association with clinicopathological parameters as well as Ki-67 expression, which is a well-known proliferative and prognostic marker in RCC. EphA2 and Ki-67 immunohistochemical staining was performed on whole sections representative of 50 patients diagnosed with primary RCC from 2013 to 2018. In addition, the association between EphA2 mRNA expression and clinicopathological parameters as well as the patients’ outcome was also evaluated using two large publicly available databases. Our results showed a significant association between EphA2 immunohistochemical expression and tumor size, nuclear grade, tumor stage, patients’ outcome and Ki-67 expression (P < .05 for all). The same trend was also observed with EphA2 mRNA expression using larger patients’ cohorts in 2 publicly available databases. Notably, EphA2 protein expression showed higher levels of co-expression with the proliferative marker Ki-67. Our results suggested that higher expression of EphA2 and Ki-67 in tumor tissues predicts a locally aggressive behaviour and poor outcome of patients with RCC. Moreover, our results give a rationale for the potential benefits of using novel therapeutic strategies with the aim of targeting EphA2 receptor in RCC patients that might help in improving their outcome.