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Open Access Research

The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging

Matthias C Schauer1, Nikolas H Stoecklein1, Joerg Theisen4, Feride Kröpil1, Stephan Baldus25, Arnulf Hoelscher3, Markus Feith4, Edwin Bölke5*, Christiane Matuschek5, Wilfried Budach5 and Wolfram Trudo Knoefel1

Author Affiliations

1 Department of General-, Visceral-, and Pediatric Surgery, Heinrich Heine Universitaet Duesseldorf, Duesseldorf, Universitätsstraße, 140225, Düsseldorf, Germany

2 Department of Pathology, Heinrich Heine Universitaet, Duesseldorf, Germany

3 General-, Visceral-, and Oncological Surgery, Universitaetsklinikum Koeln, Koeln, Germany

4 Department of Surgery, Technische Universitaet Muenchen, Munich, Germany

5 Department of Radiotherapy, Heinrich Heine University, Duesseldorf, Germany

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European Journal of Medical Research 2012, 17:10  doi:10.1186/2047-783X-17-10

Published: 14 May 2012

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.

Keywords:
E-cadherin; Ephrin B3 receptor; Esophageal adenocarcinoma; Barrett’s metaplasia