Abstract 5914: E-cadherin and beta-catenin in oral dysplasia progression

Abstract

Abstract Objectives: Epithelial-mesenchymal transition (EMT), a biological process characterized by a progressive decrease in epithelial features and increase in mesenchymal traits, has been suggested as a critical mechanism in cancer development. A defining feature of EMT is the loss of E-cadherin. Together with beta-catenin, alpha-catenin, and p120-catenin, E-cadherin forms the adherens junctions, which are involved in cell-cell adhesion of epithelial cells. As beta-catenin has both a structural and signaling role, E-cadherin potentially contributes to malignant progression via beta-catenin signaling through the Wnt pathway. E-cadherin and beta-catenin expression is altered from normal oral tissue, oral epithelial dysplasia (OED), to oral squamous cell carcinoma (OSCC), but there is no longitudinal research on the role of these biomarkers in malignant progression. The objective of this study is to explore the expression of E-cadherin and beta-catenin in OED and to determine if these expression patterns predict malignant progression. Methods: 28 progressors (PR) and 56 non-progressors (NPR) were included in this case-control study. Samples that progressed to severe OED, carcinoma in situ, or OSCC were categorized as PRs, and samples that did not progress were NPRs. Patient samples with a baseline biopsy of low-grade (mild or moderate) OED and at least 5 years of follow-up for NPRs were obtained from the Oral Cancer Prediction Longitudinal study, which has been prospectively following patients with OED for over 20 years. Immunohistochemistry (IHC) is performed on formalin-fixed paraffin-embedded tissue samples to assess for reduced membranous E-cadherin, and reduced membranous and increased cytoplasmic and/or nuclear beta-catenin expression in PRs compared to NPRs. We hypothesized that OED with this expression pattern will show greater likelihood of progression. Fisher’s exact test was used. Logistic regression will be performed to predict progression. Results: There were no significant differences in age, sex, risk of lesion site, and grade of dysplasia between PRs and NPRs. There were significant differences in length of follow-up time and smoking history. IHC has been completed on 27 samples to date, which show decreased membranous beta-catenin expression in PRs compared to NPRs (p=0.042). IHC for additional samples will be performed to assess for cytoplasmic and nuclear beta-catenin expression, and to compare expression patterns between PRs and NPRs to determine prediction of malignant progression. Conclusion: Early results suggest that membranous beta-catenin expression may be decreased in OED that progressed compared to OED that did not. This research enhances the understanding of EMT’s role in malignant progression and hopes to potentially aid in the intervention of oral lesions at risk of cancer. Citation Format: Ilena Yim, Iris Lin, Leigha Rock, Lewei Zhang, Miriam Rosin, Denise Laronde. E-cadherin and beta-catenin in oral dysplasia progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5914.