Loss of EphA3 Protein Expression Is Associated With Advanced TNM Stage in Clear-Cell Renal Cell Carcinoma

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Abstract

Micro-Abstract

Erythropoietin-producing hepatocellular carcinoma (Eph) receptors constitute the largest family of receptor tyrosine kinases. Eph receptors and their ephrin ligands play important roles in axonal guidance and cell migration during the development of the nervous system. Aberrant expression of Eph/ephrin has been detected in human tumor tissues, suggesting their involvement in tumor metastasis and invasion, and their importance in disease prognosis.

Background:

Erythropoietin-producing hepatocellular carcinoma (Eph) receptors constitute the largest family of receptor tyrosine kinases. Ephs and their ligands ephrins play an important role in development and carcinogenesis. The expression of EphA3, an Eph family member, has been investigated in a variety of human cancers, with mixed results. High levels of EphA3 protein expression have been reported in colorectal, prostate, and gastric cancers, whereas loss of protein expression has been reported in lung and hematopoietic cancers. EphA3 expression in clear-cell renal cell carcinoma (ccRCC) and its association with clinicopathological parameters has not previously been examined. The aim of this study was to determine the cancerous value of EphA3 protein expression in patients with ccRCC.

Materials and Methods:

This study included 68 patients with ccRCC. EphA3 protein expression was examined in ccRCC tissue samples using immunohistochemistry and a specific polyclonal antibody, and the correlation between EphA3 expression and clinicopathological parameters was subsequently evaluated.

Results:

High EphA3 protein expression was observed in all normal renal tubules. In the 68 ccRCC patient samples examined, EphA3 protein expression was detected in 19 cases (27.9%) and undetectable in 49 cases (72.1%). EphA3 protein expression was significantly associated with tumor diameter (P = .016) and tumor, node metastases stage (P = .029). No significant association between protein expression and sex (P = .387), age (P = .727), or nuclear grade (P = .243) was found.

Conclusion:

Ourdata indicate that EphA3 protein expression is reduced in ccRCC, suggesting the possibility that this receptor functions as a tumor suppressor in this disease.

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