Abstract
The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously. Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN). Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing doses of 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processed for histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twenty hepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferating cell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected in hepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observed in normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells, showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with co- localization. Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors and many tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-induced tumors, possibly associated with cell proliferation.
Highlights
Epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein that is expressed on most normal epithelial cells
Double staining of EpCAM and proliferating cell nuclear antigen (PCNA) Double staining of both EpCAM and PCNA showed that many tumor cells had obvious co-localization, synergistic expression was not detected in normally appearing hepatocytes (Figure 3)
EpCAM expression was not found different between hepatocellular adenomas (HCAs) and hepatocellular carcinomas (HCC)
Summary
Epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein that is expressed on most normal epithelial cells. It was first proposed to function as a cell adhesion molecule since it mediates homophilic adhesion interaction, which might prevent metastasis (Litvinov et al, 1994). EpCAM has been reported to abrogate E-cadherin-mediated cell-cell adhesion, indicating that is may have a different role in some other tumor type by promoting metastasis (van der Gun et al, 2010). EpCAM-expression in liver cells was rare in early stages of liver diseases and was increasingly prominent in later stages, consistently arrayed around the periphery of cords of hepatobiliary cells (Yoon et al, 2011). It was shown recently that EpCAM-positive cells were defined as novel prognostic subtypes of hepatocellular carcinomas (HCCs) in human (Yamashita et al, 2008). EpCAM-positive HCCs displayed a distinct molecular signature with features of hepatic progenitor cells including the presence of known stem cell markers, whereas EpCAM-negative HCCs displayed genes with features of mature hepatocytes (Yamashita et al, 2008)
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