Endocrine Pathology

, Volume 24, Issue 4, pp 206–212

The Role of Epithelial Mesenchymal Transition Markers in Thyroid Carcinoma Progression

  • Celina Montemayor-Garcia
  • Heather Hardin
  • Zhenying Guo
  • Carolina Larrain
  • Darya Buehler
  • Sofia Asioli
  • Herbert Chen
  • Ricardo V. Lloyd
Article

DOI: 10.1007/s12022-013-9272-9

Cite this article as:
Montemayor-Garcia, C., Hardin, H., Guo, Z. et al. Endocr Pathol (2013) 24: 206. doi:10.1007/s12022-013-9272-9

Abstract

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.

Keywords

Thyroid carcinomaAnaplastic thyroid carcinomaZEB1Smad7E-Cadherin

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Celina Montemayor-Garcia
    • 1
  • Heather Hardin
    • 1
  • Zhenying Guo
    • 1
  • Carolina Larrain
    • 1
  • Darya Buehler
    • 1
  • Sofia Asioli
    • 2
  • Herbert Chen
    • 3
  • Ricardo V. Lloyd
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of Wisconsin School of Medicine and Public Health, K4/436 Clinical Science CenterMadisonUSA
  2. 2.Department of Biomedical Sciences and Human OncologyUniversity of TurinTurinItaly
  3. 3.Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA