Limited suitability of EpCAM for molecular staging of tumor borders in head and neck cancer

Background: The epithelial cell adhesion molecule (EpCAM) is expressed in most normal epithelia, but is absent from squamous stratified epithelia. However, a de novo expression can be observed in squamous epithelia during carcinogenesis. Materials and Methods: In order to evaluate EpCAM as a molecular marker to indicate borders of high risk for the development of local recurrences, its expression was examined in the marginal zone of malignancies. Specimens of squamous cell carcinoma of the head and neck (SCCHN), of the histologically tumor-free defined resection margin and of healthy epithelia of 20 patients were examined by RT-PCR in order to identify the expression of EpCAM in these three different areas. Additionally, immunohistochemistry was performed on biopsies from 10 patients in order to confirm these findings and to investigate a potential correlation between EpCAM expression and the degree of dysplasia. Results: By RT-PCR, high expression of EpCAM was found in the tumor. An inverse correlation was observed between EpCAM expression and the distance from the tumor, with no expression being detectable in healthy oral mucosa. In 70% of the cases, EpCAM was expressed in the marginal zone, which had been defined as tumor-free by routine histopathological assessment. Additional immunohistology revealed no correlation between EpCAM expression and the grade of dysplasia. Conclusion: Our data provide evidence that EpCAM is restricted as a marker for redefining the real tumor margin by RT-PCR. To complement routine histology, immunohistochemical staining with EpCAM is limited due to its expression in hyperplastic tissue without dysplastic changes. Both observations limit the reliable use of EpCAM for the molecular definition of the critical tumor border and resection margins.