9541 Background: The Epithelial Cell Adhesion Molecule (EpCAM) is involved in homophillic cell-cell adhesion and proliferation in normal epithelia and is frequently over-expressed in primary and metastatic adenocarcinomas. However, it has been postulated that during detachment and dissemination of tumor cells, the antigen may of necessity be down-regulated. Circulating tumor cells (CTC) by definition, may demonstrate this phenomenon as they have successfully escaped their local microenvironment and entered the circulation. The objective of this study was to investigate this paradox.
METHODS
EpCAM expression of CTC was compared to tumor cells in paraffin embedded tissue micro-arrays containing various benign diseases and carcinomas. EpCAM expression on CTC was determined by flowcytometry (FCM) and in paraffin embedded tissue by immunohistochemistry (IHC). To permit comparison of FCM results to those derived by IHC, EpCAM was quantified on cancer cell lines by FCM and then paraffin embedded cell-blocks of these lines were used as staining guides for IHC analysis of tissue micro-arrays.
RESULTS
By IHC, 97% (384/397) of solid tissues analyzed had detectable EpCAM, with 72% of tissues showing antigen expression levels of 400,000 molecules / cell. FCM analysis of CTC from 100 metastatic carcinoma patients with >2 CTC / 90μL blood showed EpCAM expression ranging from 9,900 to 246,000 (mean 49,700) antigens per cell.
CONCLUSIONS
The ten fold lower expression of EpCAM on CTC compared to primary and metastatic tissues indicates that EpCAM expression is transient, and dependent upon the local microenvironment. This supports the hypothesis that the EpCAM molecule is down-regulated on a subset of carcinoma cells potentially to facilitate entry into and survival during transit through the circulation. [Table: see text].