E-cadherin and beta-catenin expression in oral epithelial dysplasia : predicting progression to cancer

Objectives: The epithelial-mesenchymal transition (EMT) is a biological process involved in cancer development and entails epithelial cells progressively gaining mesenchymal traits. The loss of the cell adhesion protein E-cadherin is a hallmark feature of EMT and may play a role in early malignant progression through its interaction with beta-catenin in the Wnt pathway. Expression of E-cadherin and beta-catenin is altered from normal oral tissue, oral epithelial dysplasia (OED), to oral squamous cell carcinoma (OSCC), but there is no literature on the roles of these proteins in early malignant progression. The purpose of this study was to explore E-cadherin and beta-catenin expression in OED and to determine whether such expression patterns predict malignant progression. Methods: This case-control pilot study sampled 29 progressors (PR) and 58 non-progressors (NPR) from the Oral Cancer Prediction Longitudinal study. Participants with an initial diagnosis of low-grade dysplasia OED and no previous history of oral cancer were included. PRs were participants that progressed to severe OED, carcinoma in-situ, or OSCC, while NPRs were those that did not progress. Formalin-fixed paraffin-embedded tissue sections were immunohistochemically stained to assess for low membranous E-cadherin, and low membranous and high cytoplasmic and/or nuclear beta-catenin expression in select epithelial layers (basal, parabasal, lower spinous, and upper spinous) and the entire epithelium in PRs compared to NPRs. For membranous staining, low expression was defined as negative or weak staining, while high expression was moderate or strong staining. In the cytoplasm and nucleus, low expression was defined as an absence of stain, and high expression was the presence of stain. The Mann-Whitney U, Chi-square, Fisher’s exact test, and logistic regression were used in statistical analysis. Results: The basal (P=0.55), lower spinous (P=0.62), and upper spinous layer (P=0.45) had a greater, but insignificant, proportion of progressors with low membranous E-cadherin expression. For membranous beta-catenin, the parabasal (P=0.53) and lower spinous layer (P=0.62) had a greater proportion of progressors with low expression, but again insignificant. Few samples showed cytoplasmic and/or nuclear beta-catenin staining. Conclusion: The expression patterns of E-cadherin and beta-catenin in OED did not predict malignant progression. Future research should incorporate quantitative digital analysis.Dentistry, Faculty ofGraduat