DIFFERENTIAL EXPRESSION OF E-CADHERIN IN NORMAL, METAPLASTIC AND DYSPLASTIC ESOPHAGEAL MUCOSA - A PUTATIVE BIOMARKER

Barrett's mucosa is a potentially premalignant columnar lined metaplas tic epithelium in the oesophagus about which little is known regarding maintenance of cell adhesion. In this regard E-Cadherin (E-cad) is a 120 kDa polypeptide present in all epithelial tissues and it is the pr ime mediator of cell-cell interactions. An immunohistochemical techniq ue utilised the monoclonal antibody HECD-1 to evaluate E-cad expressio n in microwave treated, paraffin embedded sections from 120 patients. The phenotype of the specimens from the patients were metaplastic [41] and dysplastic mucosa [24], invasive squamous carcinoma [15] and aden ocarcinoma [18] and corresponding metastatic lesions [10] as well as 1 2 specimens of normal oesophageal mucosae. Surface expression was high in non-metaplastic tissue and in non-dysplastic metaplasia but was re duced extensively in dysplasia. In addition in squamous carcinoma and adenocarcinoma E-cad was characteristically expressed in the cytoplasm and this was associated with poor morphological differentiation. SDS- PAGE gel protein analysis revealed the characteristic 120 kDa sized pr otein in normal squamous oesophageal tissue. In Barrett's metaplastic tissue and carcinoma, however, stronger bands at 108 kDa and 45 kDa we re also present, suggesting either decreased glycosylation or a trunca ted protein in the metaplastic and neoplastic tissue, respectively. In conclusion changes in E-cad immunoreactivity and cellular localisatio n occur in premalignant metaplastic epithelium of the oesophagus. Furt her studies are in progress to evaluate whether the abnormal E-cad pro tein reflects both loss of function and may be used as a biomarker in pre-malignant lesions.