Analogous to the findings in colon cancer, in our patients Eph B3/E-cadherin coexpression selleck chemicals is significantly correlated with a favorable tumor stage. Although E-cadherin mRNA expression and IHC positivity did not show a significant difference with regard to tumor stage, coexpression of both proteins was significantly and inversely correlated with depth of invasion, lymph node involvement and lymph node coefficient (= number of involved lymph nodes/number of removed lymph nodes). Recently in vitro analysis indicated that Eph B activation triggered redistribution of E-cadherin from the cytoplasm to the basolateral membrane without altering protein levels in a colon cancer cell line. Consequently, Eph B signaling couples cell contraction with cell-to-cell-adhesion by promoting the recruitment of E-cadherin in colon cancer [17].

This mechanism may be equally present in esophageal cancer. In our study, simultaneous expression of E-cadherin and Eph B3 was accompanied by an intracellular E-cadherin distribution comparable to that in healthy esophageal mucosal cells. A strong membranous accentuated immunohistologic reaction was seen in 10% of all patients, while we detected a fairly strong cytoplasmatic and a faint membranous staining in carcinoma cells without Eph B3 expression. Taking the in vitro analysis by Cortina into account, the above observations suggest that Eph B signaling seems to restrict the capacity of malignant cells for infiltrative growth by enforcing E-cadherin adhesion. In an ApcMin/+ mouse model the EphB mediated compartmentalization was demonstrated to be a mechanism suppressing cancer progression [17].

In a clinical study Eph B3 expression was significantly reduced in advanced Dukes�� stage tumor specimens [16]. In vitro examinations of a colon cancer cell line (HT-29) demonstrated that Eph B3/EFN interaction potentiated junctional adhesion molecules ZO-1, E-cadherin and plakoglobin, which are representatives of tight junctions and desmosomes, respectively [16]. In regard to the literature concerning the interaction between Eph B3 and E-cadherin, both proteins together have a significant tumor suppressor function. Comparable to the tumorigenesis of colon cancer we could show an altered Eph B3 and E-cadherin IHC activity of esophageal carcinoma compared to the normal mucosa and a reduced E-cadherin mRNA expression rate in esophageal carcinoma compared to normal mucosa.

In the dysplasia-carcinoma sequence Eph B3 activity is reduced and E-cadherin is dissolved in the cytoplasm. Lack of E-cadherin-mediated adhesion correlates with the loss of epithelial morphology and the acquisition of mesenchymal characteristics. In our patients with esophageal cancer we could find a significant Brefeldin_A inverse correlation between a persisting simultaneous expression of Eph B3 and E-cadherin and depth of invasion and lymph node metastasis as the strongest predictive factors for long-term survival.