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.
The University of Queensland, Centre for Clinical Research, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
Oral Oncol. 2012 Oct;48(10):997-1006. doi: 10.1016/j.oraloncology.2012.05.011. Epub 2012 Jun 14.
To investigate immunohistochemical (IHC) analysis of E-cadherin, β-catenin, APC and Vimentin for prediction of oral malignant transformation.
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.
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.
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.
研究 E-钙黏蛋白、β-连环蛋白、APC 和波形蛋白的免疫组织化学（IHC）分析在预测口腔恶性转化中的作用。
使用 IHC 评分或标记指数评分系统，对 100 例口腔活检标本进行 E-钙黏蛋白、β-连环蛋白、APC 和波形蛋白的免疫反应性测定，这些标本分为正常、轻度异型增生、中重度异型增生或 OSCC。分析生物标志物的共表达与组织病理学分级的相关性。使用 RT-PCR 进一步验证波形蛋白和 E-钙黏蛋白的结果，并在基于人真皮的新型器官型细胞侵袭模型中进行体外研究。
观察到 E-钙黏蛋白表达减少但波形蛋白表达增加，且与疾病严重程度增加相关。上皮细胞β-连环蛋白的定位从膜向细胞质/核转移，组织病理学分级严重程度增加。与正常相比，轻度异型增生的 APC 表达减少，但 OSCC 增加。β-连环蛋白、APC 和波形蛋白的共表达（Spearman 等级相关）表明这些分子的相互依赖性以及 Wnt 通路在口腔恶性转化中的参与。与正常组织相比，异型增生和 OSCC 的 E-钙黏蛋白相对 mRNA 表达小于 1%，OSCC 的 Vimentin mRNA 表达比正常高 3.7 倍。在器官型培养 63 天后，肿瘤性口腔角质形成细胞（PE/CA-PJ15）相对于上皮中的非侵袭性细胞，丧失了 E-钙黏蛋白的表达，获得了波形蛋白的表达。
EMT 标志物——E-钙黏蛋白、β-连环蛋白、APC 和波形蛋白的表达趋势表明它们通过 Wnt 通路失调参与口腔癌变。β-连环蛋白、APC 和波形蛋白的异常表达可能是恶性转化的潜在标志物。
