Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

Nikolas H Stoecklein, Annika Siegmund, Peter Scheunemann, Andreas M Luebke, Andreas Erbersdobler, Pablo E Verde, Claus F Eisenberger, Matthias Peiper, Alexander Rehders, Jan Schulte Am Esch, Wolfram Trudo Knoefel, Stefan B Hosch, Nikolas H Stoecklein, Annika Siegmund, Peter Scheunemann, Andreas M Luebke, Andreas Erbersdobler, Pablo E Verde, Claus F Eisenberger, Matthias Peiper, Alexander Rehders, Jan Schulte Am Esch, Wolfram Trudo Knoefel, Stefan B Hosch

Abstract

Background: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies.

Methods: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up.

Results: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor.

Conclusion: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention.

Figures

Figure 1
Figure 1
Ep-CAM expression in esophageal SCC. A, esophageal SCC without Ep-CAM neo-expression. B, Detail of a tumor with 2+ Ep-CAM expression. C, Tumor with heterogeneous 3+ Ep-CAM expression (white arrow: strong expression; black arrow: faint expression) and D, shows a representative sample with homogenous 3+ Ep-CAM expression.
Figure 2
Figure 2
Prognostic impact of Ep-CAM. Kaplan-Meier curves for relapse-free (A) and overall survival (B) calculated from 53 patients with esophageal SCC.

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