Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma.

Overexpression of the Eph receptor tyrosine kinases in cancers is related to malignant transformation, metastasis, tumor differentiation, and prognosis. Down-regulation of EphA7 secondary to hypermethylation has been reported in colorectal cancer. In the present study, expression of EphA7 in gastric cancer cell lines and gastric carcinoma specimens was determined by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression of EphA7 was reduced in all tested gastric cancer cell lines; however, there is marked variability in expression among gastric carcinoma specimens. Overexpression was observed more often in younger patients (aged < or =65 years) (P = .03) and in patients with advanced cancer (P = .031). Hypermethylation of the EphA7 promoter-associated CpG island was found using methylation-specific polymerase chain reaction. Down-regulation of EphA7 was significantly related to hypermethylation (P = .001), and the level of hypermethylation was greater in moderately differentiated tumors than in poorly differentiated ones (P = .03). We also performed immunohistochemical staining for EphA7 in 52 gastric carcinoma specimens and found that expression of the protein was consistent with its transcript expression, with the protein being significantly overexpressed in younger patients (P = .016) and in patients with advanced tumors (P = .033). Our data indicate that EphA7 may have roles in the pathogenesis and development of gastric carcinomas.