Epithelial to mesenchymal transition (EMT) biomarkers--E-cadherin, beta-catenin, APC and Vimentin--in oral squamous cell carcinogenesis and transformation.
OBJECTIVE
To investigate immunohistochemical (IHC) analysis of E-cadherin, β-catenin, APC and Vimentin for prediction of oral malignant transformation.


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.
The University of Queensland, School of Dentistry, 200 Turbot Street, Brisbane, Queensland 4000, Australia; The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
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Chaw
The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
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Abdul Majeed
The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
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Dalley
The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
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Chan
The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
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Stein
The University of Queensland, School of Dentistry, 200 Turbot Street, Brisbane, Queensland 4000, Australia; The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia. Electronic address: c.farah@uq.edu.au.
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Farah
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014746:Vimentin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D014746:Vimentin; D051176:beta Catenin