BMC Cancer 2006, 6:165 http://www.biomedcentral.com/1471-2407/6/165 EFpig-CurAeM1expression in esophageal SCC 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. p185, Ep-CAM is a membranous protein, and the criteria are standardized and are already used to assign patients to antibody-based therapy. The benefit or special applicabil- ity of the Hercep-Test Scoring System to evaluate EpCAM staining is so far unproven and needs to be confirmed in independent future studies. However, applying this scor- ing system, we identified three different levels of Ep-CAM expression. Interestingly, strong (3+) Ep-CAM expression was of prognostic significance. A correlation of strong Ep- CAM expression and poor prognosis has been also observed in breast cancer [15,16] and in gallbladder can- cer [17]. In SCC of the lung, strong Ep-CAM expression was positively correlated to lymph node metastasis and larger tumors, however a correlation to survival could not been demonstrated [29]. Several lines of evidence point to the importance of this molecule in the early phase of squamous cell cancer pro- gression. First, Ep-CAM de novo expression was already noted in weak, mild and severe dysplasias of squamous epithelium [14]. Second, this protein is expressed in the early phase of tumor cell dissemination and metastasis in esophageal and lung SCC, respectively. Ep-CAM expres- sion is used to identify single tumor cells that have dis- seminated to lymph nodes and are associated with a poor prognosis [24,30,31]. Their malignant genotype was recently disclosed by single cell comparative genomic hybridization [32] and our group was able to demonstrate the proliferative capacity and tumorigenicity of these cells [33]. So far, the exact mechanisms of action of Ep-CAM contrib- uting to the malignant potential of tumor cells are not Page 5 of 8 (page number not for citation purposes)