Down-regulation of EpCAM correlates with an unfavorable Prognosis in the Metaplasia-Carcinoma-Sequence of Barrett’s Carcinoma

Abstract

EpCAM represents a promising therapeutic target in antibody-based tumor therapy. In our study, we assessed the potential of EpCAM as a therapeutic molecular target in the treatment of esophageal adenocarcinoma (Barrett’s carcinoma) by analyzing the expression of EpCAM using a standardized immunohistochemistry staining assay on a tissue microarray (TMA) comprising the primary tumor tissue of 98 patients. In addition to the expression in the primary tumors, EpCAM protein expression was also determined in the normal esophageal mucosa of 26 patients and 10 cases of Barrett’s metaplasia.

Whereas no expression was detected in normal esophageal mucosa a strong (3+) EpCAM expression was detected in all cases of Barrett’s metaplasia In contrast, only 49% of the esophageal adenocarcinomas exhibited a strong (3+) staining, while 31% showed a moderate (2+) and 14% a weak (1+) EpCAM expression. In 6% of the primary growths no EpCAM expression was detected. Interestingly, the down-regulation (2+/1+/0) of EpCAM in the primary tumor tissue compared to the strong (3+) expression generally observed in Barrett’s metaplasia significantly correlated with lymph node metastasis (logrank test, p<0.01) and low differentiation (logrank test, p<0.01). At the same time, patients with a reduced expression of EpCAM in the primary tumor tissue shared a significantly shortened post-operative survival in the univariate analysis. However, the multivariate analysis revealed no independent prognostic significance of the diminished EpCAM expression compared to other histopathological parameters.

The results of our study indicate a steady neoexpression of EpCAM in the progression from normal esophageal epithelium to Barrett’s metaplasia. The negative prognostic outcome associated to the EpCAM down regulation observed in more than 50% of subsequent esophageal adenocarcinoma underlines the biological relevance of the molecule in the metaplasia-dysplasia-carcinoma sequence of Barrett’s carcinoma. Thus, EpCAM emerges as an additional marker to assess the initiation and progression of esophageal adenocarcinoma.