title: EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers.
abstract: OBJECTIVE
  To comprehensively evaluate ephrin 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.
  
  
  METHODS
  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 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 EphB2 positivity in tumors without EphB2 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 EphB2 expression serving as an indicator of the possible pathogenetic role of EphB2 signaling in the maintenance of tissue architecture of colon epithelium.
authors.affiliation: Institute of Pathology, University Hospital and Institute of Clinical Pathology, Basel, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Spichtin
authors.forename: Robert
authors.initials: R
authors.lastname: Maurer
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Jeff
authors.initials: J
authors.lastname: Kiefer
authors.forename: Pia
authors.initials: P
authors.lastname: Huusko
authors.forename: David
authors.initials: D
authors.lastname: Azorsa
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Olli-P
authors.initials: OP
authors.lastname: Kallioniemi
authors.forename: Spyro
authors.initials: S
authors.lastname: Mousses
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
mesh_terms: D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D036183:Receptor, EphB2 / Q000096:biosynthesis*; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D036183:Receptor, EphB2