EpCAM – Antibody Lexicon

Synonyms: Epithelial Cell Adhesion Molecule, epithelial antigen, epithelial specific antigen, epithelial glycoprotein, Ber-EP4, MOC31

by Assia Bassarova

Background

Epithelial cell adhesion molecule (EpCAM) is expressed on the cell membrane (preferentially basolaterally) and in the cytoplasm of most epithelial cells of the body. The EpCAM consists of two 34kDa and 39 kDa glycopolypeptides derived from the MDF-7 breast cancer cell line. It recognizes an epitope distinct from keratins or other common epithelial antigens. Prolonged formalin fixation might lead to either weak or complete loss of expression.
EpCAM has a role in cell signaling, proliferation, adhesion, migration, and differentiation. Studies have found that EpCAM expression is high in proliferating cells and low in differentiated cells. In mature tissue, EpCAM is expressed in virtually all simple epithelia, and its expression is usually not subject to change. However, the expression of EpCAM can change in epithelial progenitor cells, which are required for tissue maintenance and turnover. For instance, bipotent progenitor cells of adult human mammary tissue as well as progenitor cells expressing luminal cell markers are both EpCAM-positive. These progenitors can give rise to progenitor myoepithelial cells, which do not express EpCAM. It was also found to work as an oncogenic signaling molecule through the Wnt signaling pathway. The mechanism of EpCAM induced proliferation in cancer cells has been shown to involve regulated intracellular membrane proteolysis (RIP). Names of the popular clones like Ber-EP4 and MOC31 are used often as synonyms.

Staining in normal tissues

EpCAM is expressed on the cell membrane (preferentially basolaterally) and in the cytoplasm of most epithelial cells of the body, with the exception of squamous epithelium, hepatocytes, renal proximal tubular cells, gastric parietal cells, medullary epithelium of the thymus and myoepithelial cells. Focal positivity may be seen in the basal layer of squamous cell epithelium of endoderm (tonsil) and mesoderm (uterine cervix). Both normal and neoplastic mesothelium usually do not express EpCAM antigen but may show focal reaction undergoing reactive changes. Mesenchymal cells and cells from the neural crest are negative, with the exception of olfactory neurons.

Staining in tumors

It stains basal cell carcinoma but is negative in squamous cell carcinoma of the skin.
Most adenocarcinomas, especially high proportion of lung adenocarcinomas, are positive in majority of cases. The rate of positivity is usually lower in non-pulmonary adenocarcinomas, falling to 35-50% for renal cell carcinomas (except chromophobe variant, which is positive in 80% of cases). Mesothelioma is usually negative in 80-90% of cases.
Positive EpCAM staining is observed in desmoplastic small round cell tumors (DSRCT)

Staining pattern

Membranous (particularly basocellular) and cytoplasmic.

Control tissue

Normal lung, normal skin, normal kidney, normal liver, lung adenocarcinoma and prostate BPH.

Application

Differentiation of basal cell, squamous cell and basosquamous cell carcinoma of skin.
Differentiation of hepatocellular carcinoma from cholangiocarcinoma and metastatic adenocarcinoma.
Differentiation of mesothelioma from adenocarcinoma. The reported percentage of mesotheliomas expressing EpCAM varies rather widely. This is due to lack of consensus in assessment of EpCAM positivity (single cells vs. diffuse strong positivity in part because some authors count any single cell immunoreactivity as constituting positivity, basolateral membrane staining vs. complete membrane staining). Recommended to use in panel with e.g. Cytokeratin 5/6, Calretinin, WT-1, D2-40, CA125, TTF-1.

by Assia Bassarova

Background

Staining in normal tissues

Staining in tumors

Staining pattern

Control tissue

Application

Selected references