The Role of Epithelial Mesenchymal Transition Markers in Thyroid Carcinoma Progression

• DOI: 10.1007/s12022-013-9272-9
• Publication Date: 2013-10-14T07:06:35Z
• Authors: Celina Montemayor...; Heather Hardin; Zhenying Guo; Carolina Larrain; Darya Buehler; Sofia Asioli; Herbert Chen; Ricardo V. Lloyd
• Keywords: Adenoma; Adult; Male; Epithelial-Mesenchymal Transition; Adolescent; anaplastic thyroid carcinoma; E-Cadherin; Smad7; Thyroid carcinoma; ZEB1; Thyroid Gland; Cell Line; 03 medical and health sciences; 0302 clinical medicine; Adenocarcinoma, Follicular; Biomarkers, Tumor; Humans; Thyroid Neoplasms; Aged; Aged, 80 and over; Homeodomain Proteins; Middle Aged; Cadherins; Carcinoma, Papillary; 3. Good health; Disease Progression; Female; Transcription Factors

Understanding the molecular mechanisms involved in thyroid cancer progression may provide targets for more effective treatment of aggressive thyroid cancers. Epithelial mesenchymal transition (EMT) is a major pathologic mechanism in tumor progression and is linked to the acquisition of stem-like properties of cancer cells. We examined expression of ZEB1 which activates EMT by binding to the E-box elements in the E-cadherin promoter, and expression of E-cadherin in normal and neoplastic thyroid tissues in a tissue microarray which included 127 neoplasms and 10 normal thyroid specimens. Thyroid follicular adenomas (n = 32), follicular thyroid carcinomas (n = 28), and papillary thyroid carcinomas (n = 57) all expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic thyroid carcinomas (ATC, n = 10) were negative for E-cadherin, but positive for ZEB1. A validation set of 10 whole sections of ATCs showed 90 % of cases positive for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines (normal thyroid, NTHY-OR13-1; PTC, TPC-1, and ATC, THJ-21T) showed that the ATC cell line expressed the highest levels of ZEB1 while the normal thyroid cell line expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed that Smad7 mRNA was significantly higher in ATC than in any other group (p < 0.05). These results indicate that ATCs show evidence of EMT including decreased expression of E-cadherin and increased expression of ZEB1 compared to well-differentiated thyroid carcinomas and that increased expression of Smad7 may be associated with thyroid tumor progression.