Abstract
BackgroundTo 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.MethodsThe 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.ResultsEp-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.ConclusionOur 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.
Highlights
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
Advances in surgical techniques over the last decade improved the outcome of patients with squamous cell carcinomas (SCC) of the esophagus significantly
Expression of Ep-CAM in normal esophagus and esophageal SCC In a first step, we investigated the Ep-CAM expression in 10 normal, non-pathologic squamous epithelia of the esophagus
Summary
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. Advances in surgical techniques over the last decade improved the outcome of patients with squamous cell carcinomas (SCC) of the esophagus significantly. New adjuvant therapeutic concepts are urgently needed to eradicate effectively the minimal residual disease and to improve the post-operative prognosis of esophageal SCC patients. Tumor samples were collected from 70 patients with resectable esophageal carcinoma who had undergone radical en bloc esophagectomy at the University Hospital Hamburg Eppendorf, Germany. The survival analysis was calculated from 53 patients with R0 resection, where at least two months of prospectively evaluated clinical follow-up was available. Seventeen patients were excluded from the survival analysis because of metastatic disease (n = 5), perioperative death (n = 5), non-tumor free resection margins (n = 5) and lost for follow-up (n = 2). The clinico-pathologic data are presented in Table 1 (all patients) and in Table 2 (the 53 patients included in the survival analysis)
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