Differential Expression of the Epithelial-Mesenchymal Transition Regulator ZEB1 in Thyroid Carcinomas
Celina Montemayor-Garcia, Heather Hardin, Darya Buehler, Herbert Chen, Ricardo V Lloyd. University of Wisconsin School of Medicine and Public Health, Madison, WI
Background: The Zinc-finger E-box-binding homeobox1 (ZEB1) induces epithelial-mesenchymal transition (EMT) and down-regulates E-cadherin in epithelial cells. ZEB1 is regulated by transforming growth factor beta 1 (TGF Beta 1) and other signaling proteins. We examined the expression of ZEB1, E-cadherin, TGF Beta receptor 2 (TGFBetaR2), SMAD4 and SMAD7 in benign thyroid tissues, well differentiated and anaplastic thyroid carcinomas (ATC) by immunohistochemistry (IHC).
Design: Ten ATC, 32 follicular adenomas (FA), 28 follicular carcinomas (FTC), 57 papillary thyroid carcinomas (PTC) including 29 follicular variant of PTC, 10 multinodular goiters and 10 normal thyroids were used in a formalin-fixed paraffin-embedded tissue microarray (TMA) analysis. IHC was scored based on the percentage of cells stained. The expression of ZEB1 and E-cadherin were also analyzed by quantitative reverse transcriptase- polymerase chain reaction (QRT-PCR) in 3 cell lines- including a normal thyroid cell line, PTC and ATC cell lines.
Results: Most (6/10) ATC showed strong nuclear staining for ZEB1 while 3/10 ATC cases showed only focal staining for E- cadherin. One (1/28) FTC was positive for ZEB1, while all FTC were positive for E-cadherin. ZEB1 expression in ATC was significantly different from that in FTC (p<0.001). All cases of PTC, FA and nonneoplastic thyroids were negative for ZEB1, but positive for E-cadherin. Q RT-PCR showed the highest levels of ZEB1 mRNA expression in the ATC while E-cadherin was highest in the normal thyroid cell line.
Conclusions: The EMT regulator ZEB1 is expressed in ATC and is associated with loss of E-cadherin supporting the role of EMT in ATC. TGFBeta R2, SMAD4 and SMAD7 are expressed in benign thyroid tissues, well differentiated and ATC indicating preservation of TGFBeta1 signaling in thyroid carcinomas during EMT.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 86, Monday Morning