Abstract

Originally identified as Trop1, epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that received great attention because of its putative involvement in metastatic spread of several solid tumors including breast cancer. Experimental evidence indicated that EpCAM is a key transcriptional target of p53 tumor suppressor, due to the presence of specific p53 response elements within EPCAM gene promoter. Aim of present study was to investigate the joined prognostic significance of p53 and EpCAM in a cases series of 640 breast cancers with long-term follow-up. In addition, considering the role of EpCAM in modulating cell-cell interaction by decreasing the cytoskeleton-anchored fraction of E-cadherin, when feasible, we evaluated also E-cadherin expression. Results indicated that EpCAM overexpression was associated with a high incidence of relapse and that, when in association with p53 status, EpCAM was able to identify, within p53-positive cases, those with the highest incidence of relapse. Conversely, E-cadherin overexpression was associated with a low incidence of relapse. Overall, these findings are of particular clinical relevance taking into account the biological link between p53 activity and EPCAM gene expression and the functional relationship between EpCAM and E-cadherin in mediating cell-to-cell adhesion.

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