REDUCED EXPRESSION OF E-CADHERIN IN ORAL SQUAMOUS-CELL CARCINOMA - RELATIONSHIP WITH DNA METHYLATION OF 5'-CPG ISLAND

E-cadherin, a Ca2+-dependent cell-cell adhesion molecule, is involved in the maintenance of the epithelial phenotype. The reduction of its e xpression is considered to be important in the invasive and metastatic potential of carcinomas. A series of 52 primary oral squamous-cell ca rcinomas (SCCs) were studied immunohistochemically for E-cadherin expr ession in microwave-treated paraffin-embedded sections using a monoclo nal antibody (HECD-1). Significant correlation was found between reduc ed E-cadherin expression and tumor dedifferentiation, grade of invasiv eness, and lymph node metastasis. The possibility of E-cadherin gene m utation was also investigated by polymerase chain reaction-single stra nd conformation polymorphism (PCR-SSCP), but none was found. In additi on, to clarify the CpG methylation state around E-cadherin gene promot er in oral SCC, we examined DNA samples by PCR assay after restriction digestion with methylation-sensitive enzyme HpaII. CpG methylation wa s found in 9 (17%) of 52 primary oral SCCs, but not in the correspondi ng normal tissues. In particular, 8 of the 9 methylated cases showed r educed expression of E-cadherin and histologically diffuse invasion ty pe of tumor. These results suggest that reduction of E-cadherin expres sion is associated with the progression of human oral SCCs, and CpG me thylation of E-cadherin gene promoter causes reduction of E-cadherin e xpression in the tumor, resulting in acquisition of the invasive pheno type.