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Background:We investigated the expression of members of the epithelial cell adhesion molecule (EpCAM) signalling pathway in gastric cancer (GC) testing the following hypotheses: are these molecules expressed in GC and are they putatively involved in GC biology.Methods:The study cohort consisted of 482 patients. The following members of the EpCAM signalling pathway were analysed by immunohistochemistry and were correlated with various clinico-pathological patient characteristics: extracellular domain of EpCAM (EpEX), intracellular domain of EpCAM (EpICD), E-cadherin, β-catenin, presenilin-2 (PSEN2), and ADAM17.Results:All members of the EpCAM signalling pathway were differentially expressed in GC. The expression correlated significantly with tumour type (EpEX, EpICD, E-cadherin, β-catenin, and PSEN2), mucin phenotype (EpEX, EpICD, β-catenin, and ADAM17), T-category (EpEX, E-cadherin, and β-catenin), N-category (EpEX and β-catenin), UICC tumour stage (EpEX, EpICD, β-catenin, and PSEN2), tumour grade (EpEX, EpICD, E-cadherin, β-catenin, and PSEN2), and patients' survival (EpEX, EpICD, and PSEN2). A significant coincidental expression in GC was found for EpEX, EpICD, E-cadherin, β-catenin, PSEN2, and ADAM17. Decreased immunodetection of EpEX in locally advanced GC was not associated with decreased EpCAM mRNA levels.Conclusion:All members of the EpCAM signalling pathway are expressed in GC. The expression correlated significantly with each other and with various clinico-pathological patient characteristics, including patients' survival. Thus, the EpCAM signalling pathway is a highly interesting putative therapeutic target in GC. [ABSTRACT FROM AUTHOR]