ALTERED EXPRESSION AND FUNCTION OF E-CADHERIN IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND INVASIVE SQUAMOUS-CELL CARCINOMA

HECD-1 monoclonal antibody has been used to localize E-cadherin, a cal cium-dependent cell-cell adhesion molecule, in microwave-treated, para ffin-embedded sections from 53 cases of cervical intraepithelial neopl asia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E-c adherin was expressed on the cell membrane of basal and parabasal cell s. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were fou nd to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmi c staining was seen with worsening differentiation. Loss of membranous E-cadherin expression was also detected in 4/7 metastatic deposits. E -cadherin expression (120 kD form on Western blotting) was seen in hum an cervical carcinoma cell lines (HT3, ME180, C4I, Caski) that maintai ned the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E-cadherin-negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-nega tive cell line which showed a significant degree of cell-cell aggregat ion. These data indicate that loss of membranous E-cadherin expression may represent one of the abnormalities underlying loss of cell polari ty and differentiation which characterize CIN and invasive cervical ca ncer.