Expression of EphA1 in gastric carcinomas is associated with metastasis and survival.

Receptor tyrosine kinases of the Eph subfamily are involved in the development and the carcinogenesis of certain cancers. In this study we investigated expression of EphA1 in gastric carcinomas, and analyzed associations between EphA1 expression and clinicopathological parameters to investigate the role of EphA1 in gastric carcinoma. The level of EphA1 transcript expression in gastric carcinoma tissue and corresponding normal tissue was determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). The status of the CpG island associated with the promoter region of EphA1 was assessed by methylation-specific PCR (MSP), and EphA1 protein expression of was examined by immunohistochemical staining (IHC). Down-regulation of EphA1 transcripts was detected in 34% of the cases, up-regulation in 25% of the cases, and no difference in expression in 41% of the cases. The EphA1 transcript expression level was associated with tumor size (P=0.05), stage (P=0.001), and lymph node metastasis (P=0.011). Methylated EphA1 DNA was detected in most of the carcinomas with EphA1 down-regulation that were examined. EphA1 protein expression was associated with depth of wall invasion (P=0.069), stage (P<0.001), and lymph node metastasis (P=0.018). The survival analysis showed that patients whose tumor exhibited EphA1 up-regulation had a poorer outcome than those whose tumor exhibited down-regulation (P=0.005) or no difference in expression (P=0.003). EphA1 may have roles in invasion and metastasis by gastric carcinoma. The EphA1 expression level is a potential prognostic marker in gastric carcinoma, and the EphA1 gene may provide a novel target of therapy for gastric carcinoma.