EphA4 protein promotes invasion in clear cell renal cell carcinomas

Erythropoietin-producing hepatocellular carcinoma cell receptor A4 (EphA4) is one of the largest superfamily of human Eph receptor tyrosine kinases. The roles of EphA4 receptor in the development of nervous system have been well documented. More recently, functions of EphA4 receptor in several types of human cancer were reported with a paradoxical result. The expression and clinicopathological significance of EphA4 receptor in clear cell renal cell carcinoma (ccRCC) have not been well investigated and are unknown. In this study, a set of formalin-fixed paraffin-embedded ccRCC tissue specimens were subjected to immunohistochemistry using a specific anti-EphA4 polyclonal antibody. The relationship between EphA4 expression and clinicopathological parameters was statistically analyzed. EphA4 receptor was differentially expressed inter-specimens, which was negative (score 0) or week (score 1) staining in 34 out of 56 (60.7%), moderate (sore 2) in 12 out of 56 (21.4%) and strong (score 3) in 10 out of 56 (17.9%) ccRCC specimens. Expression level of EphA4 was positively associated with primary tumor (pT) stage (P<0.001, r =0.611) and tumor-node-metastasis (TNM) stage (P<0.001, r =0.661). Strikingly, strong expression of EphA4 was observed in tumors that invading into renal veins. No relationship between EphA4 expression and Fuhrman nuclear grade, tumor size, age and sex was found. Our data suggest that EphA4 protein promotes ccRCC tumor cell invasion and may function in progression and metastasis of ccRCC. EphA4 may be used as a potential molecular marker for prognosis.