2021 Funded Project
CFDHRE Peer Reviewed Grant
E-cadherin and beta-catenin in the malignant progression of oral epithelial dysplasia
Denise Laronde, DipDH, BA, MSc, PhD, DHP(C)
University of British Columbia
BC Cancer Research Centre/BC Cancer
Epithelial-mesenchymal transition (EMT), a biological process characterized by a progressive decrease in epithelial features and increase in mesenchymal traits,
has been proposed as a critical mechanism in cancer development. The loss of E-cadherin, a cell-surface protein involved in epithelial cell-cell adhesion, is a
hallmark feature of EMT. A potential mechanism in which E-cadherin contributes to malignant progression is via beta-catenin signaling through the Wnt pathway. Cross-sectional studies have shown that E-cadherin and beta-catenin expression is altered from normal oral mucosa, oral epithelial dysplasia (OED), to oral
squamous cell carcinoma (OSCC). However, there has been no longitudinal research on the potential role of these biomarkers in malignant progression.
1. To explore the expression of E-cadherin and beta-catenin in OED that progressed to oral cancer.
2. To determine if E-cadherin and beta-catenin expression patterns predict the progression of OED to oral cancer
Patient samples with a baseline biopsy of low-grade (mild or moderate) OED will be obtained from the Oral Cancer Prediction Longitudinal study for this matched
case-control study of 78 non-progressors and 39 progressors. Samples that progressed to severe OED, carcinoma in situ, or OSCC will be designated as
progressors, and samples that did not progress will be non-progressors. Immunohistochemistry will be performed on formalin-fixed paraffin-embedded
tissue samples to visualize expression patterns of E-cadherin and beta-catenin. Multivariate logistic regression will determine whether reduced epithelial
expression of E-cadherin, and reduced membranous and increased cytoplasmic and/or nuclear expression of beta-catenin predict malignant progression.
This research will enhance the understanding of EMT’s role in the malignant progression of oral potentially malignant lesions. This project can ultimately aid in the prevention and early identification of lesions at risk of progression to cancer and improvement of patient prognosis in a clinical setting.