BMC Cancer 2006, 6:165 http://www.biomedcentral.com/1471-2407/6/165 PFrigougnroes2tic impact of Ep-CAM Prognostic impact of Ep-CAM. Kaplan-Meier curves for relapse-free (A) and overall survival (B) calculated from 53 patients with esophageal SCC. fully understood. However, recently in vivo experiments gave the first proof of a direct link between Ep-CAM and cell cycle control. Münz et al. were able to show that upon Ep-CAM overexpression c-myc is rapidly upregulated [34]. Ep-CAM overexpression resulted in decreased growth fac- tor requirement, enhanced metabolic activity and colony formation capacity. Importantly, expression of Ep-CAM anti-sense mRNA reversed these actions and led to a strong decrease in proliferation and metabolism. How- ever, it is necessary to note in this context that functions and actions of Ep-CAM in cancer progression may differ in different cancer types. Although Ep-CAM expression is low in normal gastric mucosa and an increasing expres- sion was observed in intestinal metaplasia, loss of Ep- CAM expression is a strong prognostic factor for poor sur- vival in gastric cancer [35]. In renal cancer, loss of Ep-CAM expression was correlated with larger tumors and the pres- ence of metastases. A positive Ep-CAM expression of the renal tumor cells was an independent prognostic marker for improved survival [36]. The biology behind these observations can be explained by in vitro and in vivo exper- iments demonstrating reduced motility, invasiveness and metastatic capability of Ep-CAM transfected cells [9,11,37]. These opposed findings in the different tumor types suggest a complex role of the Ep-CAM molecule, which functions might be regulated by the different pre- dominant histogenetic molecular pathways. Since in esophageal SCC Ep-CAM is overexpressed, its expression is associated with poor prognosis and its onco- genic potential in vitro render Ep-CAM an attractive mole- cule for adjuvant targeted therapy in this cancer. As a matter of fact, in patients with Dukes C colon cancer the administration of edrecolomab, a monoclonal murine IgG1 antibody directed against Ep-CAM, following the surgical tumor resection significantly improved overall survival by reducing the risk of tumor recurrence [38]. But this murine antibody rapidly looses its efficiency in humans due to neutralization by anti-edrecolomab anti- bodies [39] and other multicenter studies did not find beneficial effects on patients survival [40,41]. However, meanwhile, a fully humanized anti-Ep-CAM antibody (MT201) was developed and its efficacy of antigen dependent cellular cytotoxicity is by two orders of magni- tude higher than that of edrecolomab [39]. More recently, Schlereth et al. reported about the very high antitumor efficacy of a bispecific single-chain antibody directed against Ep-CAM and CD3, which enables the efficient redirection and activation of tumor-resident T-cells [42]. Although we are aware, that our results of Ep-CAM expres- sion in 70 esophageal SCC are somewhat preliminary and must be confirmed by a larger independent tumor collec- tive, they are the first indication for a role of Ep-CAM in esophageal SCC progression. Neo-expression of Ep-CAM is a frequent event in this cancer and strong expression defines a subgroup with high risk for tumor relapse after complete tumor removal. Thus, Ep-CAM testing and application of therapeutic anti-EpCAM antibodies to suit- able candidates represents a chance to improve the prog- Page 6 of 8 (page number not for citation purposes)