Predictive Value of EphA2 and EphrinA-1 Expression in Oesophageal Squamous Cell Carcinoma

Abstract

The aim of this study was to analyse the protein and mRNA expressions of EphA2 and EphrinA-1 in oesophageal squamous cell carcinomas and to explore their clinicopathological associations and predictive values in oesophageal squamous cell carcinoma. Tissue array and immunohistochemistry were used to assess the protein expressions of EphA2 and EphrinA-1 in tumours from 173 patients with oesophageal squamous cell carcinoma. Paraffin sections from 20 cases in which the tumours showed variable EphA2 and EphrinA-1protein expressions were used for laser capture microdissection and processed for RT-PCR detection of EphA2 and EphrinA-1 mRNA. Among the173 oesophageal squamous cell carcinomas, 33 (19.1%) were negative, 44 (25.4%) weakly-positive, 58 (33.5%) moderately-positive and 38 (22.0%) strongly-positive for EphA2 immunostaining. For EphrinA-1 protein expression, 27 tumours (15.6 %) were negative, 41 (23.7 %) weakly-positive, 80 (46.2 %) moderately-positive and 25 (14.5%) strongly-positive. EphA2 and EphrinA-1 were often co-localized in the same tumour areas and vascular endothelial cells. Variable amounts of EphA2 and EphrinA-1 mRNAs were observed in the 20 tumours analysed. No significant association was observed between EphA2 and EphrinA-1 protein expressions and age, tumour location, tumour size, histological differentiation or clinical stage. However, there was a significant correlation between EphA2 expression and lymph node metastases (p<0.001). In univariate analysis, high levels of EphA2/EphrinA-1 protein expression, higher number of lymph node metastasis, higher histological grade and clinical stage were significantly associated with shorter overall survival. In Cox multivariate analysis, only EphA2, number of lymph node metastasis and clinical stage were of independent significance. We conclude that EphA2 protein expression is confirmed to be of predictive value for unfavourable survival for oesophageal cancer patients and may be a good target for oesophageal cancer therapy.