Epithelial to Mesenchymal Transition (EMT) in Oral Carcinogenesis

Objectives: To analyse the immunohistochemical (IHC) expression patterns of E-cadherin, β-catenin, APC and Vimentin in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). We also aim to investigate the ability of these molecules to predict malignant transformation and offer a prognostic advantage. Methods: 100 oral biopsy specimens classified as normal, mild dysplasia, moderate-severe dysplasia or OSCC were stained for E-cadherin, β-catenin, APC and Vimentin using standard IHC techniques. Immunoreactivity was determined using the IHC scoring system for E-cadherin, β-catenin and APC, and label index scoring system for Vimentin. Correlations between biomarker expression patterns and histopathological grading, and co-expression of biomarkers were analysed using the Mann-Whitney test and Spearman correlation test respectively. P-values of <0.05 were considered significant. Results: E-cadherin expression decreased from normal oral mucosa to dysplasia to OSCC; however differences were not significant. β-catenin expression was mainly localised to epithelial cell membranes in normal oral mucosa, and membranous β-catenin expression was significantly reduced in OSCC tissues. When compared to normal oral mucosa, a significant increase in cytoplasmic/nuclear β-catenin was noted in moderate-severely dysplastic tissues and OSCC. APC expression decreased from normal oral mucosa to mild dysplasia; but increased from mild dysplasia to moderate-severe dysplasia to OSCC. Vimentin expression was found to significantly increase from normal oral mucosa to dysplasia to OSCC. Significant correlations were noted between β-catenin, APC and Vimentin expression patterns, suggesting interdependence of these molecules, and the involvement of the Wnt pathway (to which the three markers belong) in oral cancer development. Conclusions: Trends in the expression of EMT markers – E-cadherin, β-catenin, APC and Vimentin – suggest that these molecules are likely to be involved in oral carcinogenesis, by means of Wnt pathway dysregulation. In potentially malignant oral lesions, aberrant expression of β-catenin, APC and Vimentin may be markers of malignant transformation.