Nuclear translocation of ß-catenin synchronized with loss of E-cadherin in oral epithelial dysplasia with a characteristic two-phase appearance.

AIMS: One of the important histopathological characteristics of oral epithelial dysplasia is a two-phase appearance of rete processes, comprising an upper layer of keratinized cells and a lower layer of basaloid cells, and thereby creating a sharp contrast between these two separate cell populations. The aim of this study was to determine the cellular adhesion status of the basaloid cells. METHODS AND RESULTS: Immunohistochemistry for ß-catenin, E-cadherin and their related molecules was carried out in surgical specimens of two-phase epithelial dysplasia of the oral mucosa. The lower-half basaloid cells and the upper keratinized cells were microdissected separately, and extracted DNA samples were subjected to methylation-specific polymerase chain reaction amplification for E-cadherin. ß-Catenin was immunolocalized within the nuclei and cytoplasm of Ki67-positive lower-half basaloid cells, as well as on the cell membrane of upper parakeratotic cells. The basaloid cells of the lower-half were also positive for matrix metalloproteinase-7 and cyclin D1, ß-catenin target gene products, α-dystroglycan, tenascin-C, and perlecan, but not for E-cadherin. The promoter region of the E-cadherin gene was hypermethylated. CONCLUSIONS: The solid proliferation of lower-half E-cadherin-free basaloid cells is enhanced by Wnt signalling cascades, as well as by the intraepithelial extracellular matrix or its bound growth factors.