Epithelial Cell Adhesion Molecule (EpCAM) has been discovered as one of the 
first tumor-specific antigens overexpressed in epithelial cancer. The present 
review focuses on the role of EpCAM in physiology and homeostasis of epithelia. 
Recent research pointed to a close interaction of EpCAM with other cell-cell 
contact molecules like E-cadherin and claudins and an intimate crosstalk with 
Wnt and TGF-beta signaling in the regulation of cell growth. Moreover, EpCAM has 
been shown to modulate trans-epithelial migration processes of white blood 
cells. Mutations of the EpCAM gene lead to disturbances of epithelial 
homeostasis and cellular differentiation from the stem cell compartment. In the 
intestinal tract EpCAM mutations contribute to congenital tufting enteropathy. 
Regarding tumorigenesis EpCAM can act as an oncogene still depending on 
additional driver mutations and epithelial phenotype of tumor cells. Tumor cells 
display increased EpCAM expression that often correlates with the loss of strict 
basolateral localization. Many tumors show enhanced regulated intramembrane 
proteolysis (RIP) of EpCAM and loose EpCAM expression under conditions of 
epithelial to mesenchymal transition. The resulting extracellular EpEX and 
intracellular EpICD fragments mediate proliferative signals to the cell. 
Resulting fragments can be validated either by sensitive enzyme-linked 
immune-sandwich assays (EpEX) or by immunohistochemistry (EpICD). The present 
review gives an overview on the detection of EpCAM fragments as predictive 
markers for disease progression and survival of cancer patients.