EphA2 Overexpression Is Associated With Lack of Hormone Receptor Expression and Poor Outcome in Endometrial Cancer

BACKGROUND: EphA2 is a tyrosine kinase receptor in the ephrin family that is implicated in oncogenesis and angiogenesis. The objective of the current investigation was to study the role of EphA2 in endometrial cancer and its relation to steroid hormone receptor expression. METHODS: EphA2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 expression levels were evaluated using immunohistochemistry in 139 endometrioid endometrial carcinoma (EEC) samples and in 10 benign endometrial samples. Samples were scored by 2 investigators who were blinded to clinical outcome. The results were correlated with clinicopathologic characteristics using univariate and multivariate analysis. A P value <.05 was considered statistically significant. RESULTS: High expression of EphA2 was detected in 48% of EEC samples versus 10% of benign samples. EphA2 overexpression was associated significantly with high disease stage (P=.0-4), high tumor grade (P=.003), increased depth of myometrial invasion (P=.05), low ER expression (P=.01), low PR expression (P=.006), and high Ki-67 expression (P=.04). Low ER and PR expression levels were associated with high tumor grade, positive lymph nodes, high Ki-67 expression, and high EphA2 expression. On univariate analysis of all patients, high EphA2 expression was associated significantly with shorter disease-specific survival (DSS) (P<.001). On multivariate analysis, age (P<.001), high disease stage (P=.002), and high EphA2 expression (P=.04) were independent predictors of poor DSS. CONCLUSIONS: EphA2 overexpression was associated with aggressive phenotypic features in EEC and was associated inversely with ER and PR expression. Thus, EphA2 may be an important therapeutic target, especially in patients with hormone receptor-negative endometrial carcinoma. Cancer 2009;115:2684-92. (C) 2009 American Cancer Society.