EphB2 expression across 138 human tumor types in a tissue microarray: High levels of expression in gastrointestinal cancers

Purpose: To comprehensively evaluate ephrlin receptor B2 (EphB2) expression in normal and neoplastic tissues. EphB2 is a tyrosine kinase recently implicated in the deregulation of cell-to-cell communication in many tumors. Experimental Design: EphB2 protein expression was analyzed by immunohistochemistry on tissue microarrays that included 76 different normal tissues, > 4,000 samples from 138 different cancer types,and 1,476 samples of colon cancer with clinical follow-up data, Results: We found most prominent EphB2 expression in the intestinal epithelium (colonic crypts) with cancer of the colorectum displaying the highest EphB2 positivity of all tumors. Positivity was p found in 100% of 118 colon adenomas but in 33.3% of 45 colon carcinomas. EphB2 expression was also observed in 75 tumor categories, including serous carcinoma of the endometrium (34.8%), adenocarcinoma of the esophagus (33.3%), intestinal adenocarcinoma of the stomach (30.2%), and adenocarcinoma of the small intestine (70%). The occasional finding of strong Eph B2 positivity in tumors without Eph B2 positivity in the corresponding normal cells [adenocarcinoma of the lung (4%) and pancreas (2.2%)] suggests that deregulation of EphB2 signaling may involve up-regulation of the protein expression. In colon carcinoma, loss of EphB2 expression was associated with advanced stage (P < 0.0001) and was an indicator of poor overall survival (P =,0.0098). Conclusions: Our results provide an overview on the EphB2. protein expression in normal and neoplastic tissues. Deregulated EphB2 expression may play a role in several cancer types with loss of Eph B2 expression serving as an indicator of the possible pathogenetic role of EphB2 signaling-in the, maintenance of tissue architecture of colon epithelium.