Expression of Ep-CAM in normal, regenerating, metaplastic, and neoplastic liver

Ep-CAM is a hemophilic, Ca2+-independent cell-cell adhesion molecule that i s expressed in many human epithelial tissues. Its increased expression is c losely associated with active cell proliferation. Furthermore, in epithelia l cell types that in adults lack Ep-CAM (i.e. squamous epithelia), up-regul ation of Ep-CAM coincides with the early stages of neoplastic change. This study has analysed the expression of Ep-CAM in liver, in the hepatocytes an d tells of the biliary duct system, in relation to proliferative diseases a nd carcinogenesis. Adult hepatocytes are Ep-CAM negative, with only bile du ct epithelium being positive in the liver tissue. However, in the 8-week em bryonic liver, the majority of hepatocytes express Ep-CAM. During regenerat ion and repair of liver tissues associated with focal nodular hyperplasia a nd (biliary) cirrhosis, activation of Ep-CAM expression was observed, with high expression levels in so-called 'ductular proliferations'-regenerating stem cells. During precursor cell differentiation into mature hepatocytes, several intermediate morphological stages could be observed, all Ep-CAM pos itive, including cells morphologically close to mature hepatocytes. Full ma turation of the precursor resulted in the disappearance of Ep-CAM expressio n. The results suggest that expression of Ep-CAM is a prerequisite of the p roliferative phenotype during differentiation of hepatocyte precursors. In liver neoplasia, Ep-CAM was expressed in almost all cholangiocarcinomas (10 /11), whereas the majority of hepatocellular carcinomas (8/10) mere negativ e, suggesting that malignant proliferation of hepatocellular carcinoma cell s is not related to expression of Ep-CAM: and that hepatocellular carcinoma originates from a highly differentiated precursor. The results indicate th at Ep-CAM can be used as an additional immunohistochemical marker to distin guish cholangiocarcinoma from hepatocellular carcinoma due to the different ial expression of Ep-CAM in these tumours. Copyright (C) 1999 John Wiley & Sons, Ltd.