title: The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging.
abstract: BACKGROUND
  In intestinal epithelium, tyrosine kinase receptor Ephrin B3 (Eph B3) maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Eph B3 is linked to colorectal cancer initiation, overexpression of Eph B3 in cancer cell lines inhibits growth and induces functional changes with decreased mesenchymal and increased epithelial markers. In order to study this tumor suppressor activity of Eph B3 in esophageal adenocarcinoma we analyzed the simultaneous expression of Eph B3 and E-cadherin in both the healthy esophagus and in Barrett's carcinoma.
  
  
  METHODS
  Simultaneous expression of Eph B3 and E-cadherin was investigated in samples from 141 patients with Barrett's carcinoma and from 20 healthy esophagi using immunhistology and quantitative PCR. Results from healthy squamous epithelium, Barrett's metaplasia and staging-specific esophageal adenocarcinoma were correlated.
  
  
  RESULTS
  A significantly reduced E-cadherin mRNA expression could be detected in adenocarcinoma compared to dysplasia. The immunhistological activity of E-cadherin and Eph B3 was reduced in adenocarcinoma compared to dysplasia or healthy esophageal mucosa. The intracellular E-cadherin distribution changed significantly from the cytoplasm to the membrane, when the Eph receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Eph B3 showed a significant inverse correlation to tumor stage.
  
  
  CONCLUSIONS
  We present novel evidence of the tumor suppressor activity of Eph B3 in esophageal adenocarcinoma possibly due to the impact on redistribution of cellular E-cadherin to the membrane. Our results suggest that this effect might play a role in the dysplasia-adenocarcinoma sequence, the infiltrative growth pattern and the development of lymph node metastases.
authors.affiliation: Department of Radiotherapy, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Schauer
authors.forename: Nikolas H
authors.initials: NH
authors.lastname: Stoecklein
authors.forename: Joerg
authors.initials: J
authors.lastname: Theisen
authors.forename: Feride
authors.initials: F
authors.lastname: Kröpil
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
authors.forename: Arnulf
authors.initials: A
authors.lastname: Hoelscher
authors.forename: Markus
authors.initials: M
authors.lastname: Feith
authors.forename: Edwin
authors.initials: E
authors.lastname: Bölke
authors.forename: Christiane
authors.initials: C
authors.lastname: Matuschek
authors.forename: Wilfried
authors.initials: W
authors.lastname: Budach
authors.forename: Wolfram Trudo
authors.initials: WT
authors.lastname: Knoefel
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D036389:Ephrin-B3 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D036081:Receptors, Eph Family / Q000378:metabolism*
chemical_list: D015820:Cadherins; D036389:Ephrin-B3; D036081:Receptors, Eph Family