Neoexpression of EpCAM in Esophageal Squamous Cell Carcinoma — Prognostic Marker and Potential Therapeutic Target

EpCAM represents a relevant therapeutic target in antibody-based tumor therapy. In our study, we investigated the potential of EpCAM as a therapeutic molecular target in the treatment of esophageal squamous cell carcinoma (ESCC) by assessing the expression of EpCAM using a tissue microarray (TMA) comprising the primary tumor tissue of 118 patients. The EpCAM protein expression in the tumors was analyzed by immunohistochemistry and verified by quantitative real-time PCR in a subgroup of cases. Whereas no expression was detected in normal esophageal squamous epithelium, 64% of the investigate tumors expressed EpCAM on a low 1+(12%), moderate 2+(19%), and strong 3+ (32%) level, respectively. Expression was predominantly heterogeneous, while subgroup exhibited an enhanced EpCAM expression at the tumor invasion front. Strong (3+) expression of EpCAM in the primary tumor tissue correlated significantly with a limited overall survival of the patients (logrank test, p=0.0479). Aside from invasion depth (pT) and nodal involvement (pN), strong (3+) expression of EpCAM in the primary tumor was established as an independent progrnostic marker in the multivariate analysis. Consistently, strong (3+) EpCAM protein expression in the tumor tissue correlated with an increased detection of the transcript in the corresponding subset of cases as determined by qPCR. Thus, the prognostic relevance of its overexpression strongly suggests EpCAM as a promising molecular target for antibody-based adjuvant therapy in ESCC.