e14527 Background: In intestinal epithelium tyrosine kinase receptor Ephrin B3 maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Ephrin B3 is linked to colorectal cancer initiation, overexpression of Ephrin 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 Ephrin B3 in esophageal adenocarcinoma we analysed the simultaneous expression of Ephrin B3 and E-cadherin in healthy esophagus and Barrett’s carcinoma. Methods: Simultaneous expression was investigated in samples of 141 patients with Barrett’s carcinoma and of 20 healthy esophagi. For analysis immunhistology and quantitative PCR was used. Results of healthy squamous epithelium, Barrett’s metaplasia and staging specific esophageal adenocarcinoma were correlated. Results: A significantly reduced E-cadherin mRNA activity in adenocarcinoma compared to dysplasia could be detected. Immunhistological activity of E-cadherin and Ephrin 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 Ephrin receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Ephrin B3 showed a significant inverse correlation to tumorstage. Conclusions: We present first evidence of the tumor suppressor activity of Ephrin B3 receptor 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.
The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging