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The Role of Epithelial Mesenchymal Transition Markers in Thyroid Carcinoma Progression

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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.

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Acknowledgments

The authors would like to thank Dr. J Copland at the Mayo Clinic Jacksonville for the THJ-21T cell line, and the Translational Research in Pathology Lab at the UW School of Medicine for the TMA construction and immunohistochemistry analyses. The study was supported by NIH-R01 CA121115 and American Cancer Society MEN2 Thyroid Cancer Professorship (HC) and CCSG P30 CA014520-39(RVL).

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The authors declare no disclosures or conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, K4/436 Clinical Science Center, Box 8550, 600 Highland Avenue, Madison, WI, 53792, USA

    Celina Montemayor-Garcia, Heather Hardin, Zhenying Guo, Carolina Larrain, Darya Buehler & Ricardo V. Lloyd

  2. Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy

    Sofia Asioli

  3. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Herbert Chen

Authors
  1. Celina Montemayor-Garcia
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  2. Heather Hardin
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  3. Zhenying Guo
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  4. Carolina Larrain
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  5. Darya Buehler
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  6. Sofia Asioli
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  7. Herbert Chen
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  8. Ricardo V. Lloyd
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Corresponding author

Correspondence to Ricardo V. Lloyd.

Additional information

This work was presented in part at the 102nd US and Canadian Academy of Pathology Annual Meeting, Baltimore Maryland, March 1–8, 2013.

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Montemayor-Garcia, C., Hardin, H., Guo, Z. et al. The Role of Epithelial Mesenchymal Transition Markers in Thyroid Carcinoma Progression. Endocr Pathol 24, 206–212 (2013). https://doi.org/10.1007/s12022-013-9272-9

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