High expression of EphA4 is associated with invasion and lymph node metastasis in colorectal carcinomas.

Eph receptors and ephrin ligands have been implicated in development of embryo, especially in vascular and nervous system. Increasing evidence suggests that Eph/ephrin signaling plays important roles in carcinogenesis. EphA4 is a member of Eph receptors and its role has been found in development of nerve and in tumorigenesis. Till now, EphA4 expression and its clinical significance in colorectal carcinoma have not been well investigated. In the present study, a set of 102 colorectal carcinoma tissue specimens were subjected to immunohistochemistry by using a specific polycolonal antibody for EphA4. Expression of EphA4 protein was more often detected in colorectal carcinoma than in normal mucosa (<0.001). High expression of EphA4 protein in colorectal carcinomas was positively associated with tumor size (=0.008, =0.260), depth of invasion (=0.004, =0.286), lymph node metastasis (=0.013, =0.244), and TNM stage (=0.005, =0.279), and was negatively associated with age of patients (=0.027, =-0.219). No significant relationship between expression of EphA4 and sex and tumor location was found. The survival analyses showed that patients whose carcinoma exhibited high expression of EphA4 had a poor outcome (=0.006). Our results suggest that EphA4 play a role in the invasion and lymph node metastasis of colorectal carcinoma. The EphA4 protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the EphA4 gene may provide a novel target for therapy of colorectal carcinoma.