Epithelial to mesenchymal transition (EMT) biomarkers – E-cadherin, beta-catenin, APC and Vimentin – in oral squamous cell carcinogenesis and transformation

Chaw, S. Y., Abdul Majeed, A., Dalley, A. J., Chan, A., Stein, S. and Farah, C. S. (2012) Epithelial to mesenchymal transition (EMT) biomarkers – E-cadherin, beta-catenin, APC and Vimentin – in oral squamous cell carcinogenesis and transformation. Oral Oncology, 48 10: 997-1006. doi:10.1016/j.oraloncology.2012.05.011


Author Chaw, S. Y.
Abdul Majeed, A.
Dalley, A. J.
Chan, A.
Stein, S.
Farah, C. S.
Title Epithelial to mesenchymal transition (EMT) biomarkers – E-cadherin, beta-catenin, APC and Vimentin – in oral squamous cell carcinogenesis and transformation
Journal name Oral Oncology   Check publisher's open access policy
ISSN 1368-8375
1741-9409
Publication date 2012-10-01
Sub-type Article (original research)
DOI 10.1016/j.oraloncology.2012.05.011
Volume 48
Issue 10
Start page 997
End page 1006
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Pergamon
Language eng
Formatted abstract
Objectives: To investigate immunohistochemical (IHC) analysis of E-cadherin, β-catenin, APC and Vimentin for prediction of oral malignant transformation.
Materials and methods: Immunoreactivity for E-cadherin, β-catenin, APC and Vimentin were determined for 100 oral biopsies classified as normal, mild dysplasia, moderate-severe dysplasia or OSCC, using the IHC scoring or label index scoring systems. Co-expression of biomarkers and correlation with histopathological grading was analysed. Vimentin and E-cadherin results were confirmed by RT-PCR and further investigated in vitro using a novel organotypic cell invasion model based on human dermis.
Results: A trend for decreased E-cadherin expression but increased Vimentin expression that correlated with increased disease severity was observed. Epithelial β-catenin localisation shifted from being membranous to cytoplasmic/nuclear with increased histopathological grade severity. Relative to normal, APC expression was decreased for mild dysplasia but increased for OSCC. Co-expression of β-catenin, APC and Vimentin (Spearman rank correlation) suggests interdependence of these molecules and involvement of the Wnt pathway in oral malignant transformation. Relative mRNA expression of E-cadherin for dysplasia and OSCC were less than 1% of normal tissue values, and mRNA expression of Vimentin was 3.7 times higher for OSCC than normal. After 63 days of organotypic culture neoplastic oral keratinocytes (PE/CA-PJ15) lost expression of E-cadherin and gained expression of Vimentin relative to their non-invasive counterparts in the epithelium.
Conclusions: Trends in the expression of EMT markers – E-cadherin, β-catenin, APC and Vimentin – suggest their involvement in oral carcinogenesis via Wnt pathway dysregulation. Aberrant expression of β-catenin, APC and Vimentin are potential markers of malignant transformation.
Keyword Oral epithelial dysplasia
Malignant transformation
Epithelial to mesenchymal transition
Immunohistochemistry
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Dentistry Publications
 
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Created: Tue, 16 Oct 2012, 05:04:10 EST by Mr Andrew Dalley on behalf of UQ Centre for Clinical Research