Epithelial cell adhesion molecule expression (CD326) in cancer: a short review.

Epithelial cell adhesion molecule (EpCAM, CD326) is a pleiotropic molecule that potentially offers therapeutic applications in cancer treatment. Initially described as a dominant surface antigen on human colon carcinoma, it is a transmembrane glycoprotein mediating epithelial-specific intercellular cell-adhesion. Recent data suggest that EpCAM is also involved in cell signaling, migration, proliferation and differentiation. Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker. Testing for EpCAM is based on morphology and phenotypical staining and can be performed with primary carcinoma tissue and cells harvested from malignant effusions. Stable or highly expressed EpCAM has been detected in most adenocarcinomas and has also been found in metastases, malignant effusions, and cancer stem cells. EpCAM may thus be an ideal tumor antigen candidate to detect circulating and metastasizing cancer cells by microchip technologies. In certain tumor types overexpression was linked to advanced stage of disease and worse overall survival, suggesting EpCAM as a potential prognostic marker. In addition to its diagnostic and prognostic role, EpCAM's broad expression and apparent involvement in tumorigenesis and metastasis point to its potential as a target for immunotherapeutic strategies. The first EpCAM targeting, trifunctional antibody catumaxomab (Removab®) has shown clear clinical benefits in treatment of malignant ascites associated with EpCAM positive carcinomas. Further research and clinical studies should unravel EpCAM's complex role in oncological processes, and expand potential therapeutic applications of EpCAM targeted strategies.

Cell discohesion and multifocality of carcinoma in situ of the bladder: new insight from the adhesion molecule profile (e-cadherin, Ep-CAM, and MUC1).

Urothelial cell carcinoma in situ (CIS) of the bladder is a superficially diffusive and highly discohesive disease. The authors analyzed the expression of some adhesion molecules (e-cadherin and Ep-CAM) and MUC1 in 32 unifocal and multifocal bladder urothelial cell CIS in an attempt to clarify this discohesion. E-cadherin was strongly expressed, in more than 75% of the cases. The presence of methylation of the CDH1 e-cadherin promoter gene was also investigated, but methylation was found in only one case. Ep-CAM was present in all the cases with a heterogeneous staining pattern. Similarly, MUC1/episialin was variously present in 94% of the cases without a polarized staining pattern and was expressed more strongly in cases with multifocal disease. Because loss of MUC1 polarization leads to interference with cell-cell adhesion mechanisms mediated by cadherins, these findings help explain why bladder urothelial cell CIS often shows a discohesive morphology and multifocality despite a strongly expressed adhesion molecule profile. Finally, Ep-CAM expression might provide some support for future target therapy trials.