Expression of EphA2 and EphrinA-1 in vulvar carcinomas and its relation to prognosis

Abstract

Aims: To examine the expression of EphA2 and EphrinA-1 in vulvar squamous cell carcinomas and investigate their prognostic relevance.

Methods: Tumors from 224 patients with vulvar squamous cell carcinomas were investigated for expression of EphA2 and EphrinA-1 using single and double immunostaining methods.

Results: High expression (strong/moderate staining intensity) of EphA2 and EphrinA-1 was observed in 114 (51%) and 126 (56%) vulvar carcinomas, respectively. In the three cases tested using double immunostaining method colocalization of EphA2 and EphrinA-1 proteins were identified in the same neoplastic cells. High EphA2 expression was significantly correlated to high expression of EphrinA-1 (P < 0.01) and cyclin A (P < 0.01), large tumor size (P = 0.03), deep invasion (P < 0.01) and higher FIGO stage (P = 0.05). A correlation between high EphrinA-1 expression and high levels of cyclin A (P < 0.01) and p21 (P < 0.01), deep invasion (P < 0.01) and higher FIGO stage (P = 0.01) was also seen. In univariate analysis, high expression of EphrinA-1 was associated with poor survival (P = 0.03). However, in the multivariate analysis neither EphrinA-1 nor EphA2 were significantly correlated to survival.

Conclusions: EphA2 and EphrinA-1 are overexpressed in 51% and 56% of the vulvar squamous cell carcinomas, respectively, and high levels of EphA2 and EphrinA-1 proteins are associated with deep tumor invasion and high FIGO stage. However, EphA2 and EphrinA-1 are not independently associated with clinical outcome in vulvar carcinomas.