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. 2013 Jan;26(1):54-61.
doi: 10.1038/modpathol.2012.137. Epub 2012 Aug 17.

Expression of epithelial-mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas

Darya Buehler  1 , Heather Hardin, Weihua Shan, Celina Montemayor-Garcia, Patrick S Rush, Sofia Asioli, Herbert Chen, Ricardo V Lloyd
Affiliations

Expression of epithelial-mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas

Darya Buehler et al. Mod Pathol. 2013 Jan.

Abstract

Epithelial-mesenchymal transition is an important mechanism of epithelial tumor progression, local invasion and metastasis. The E-cadherin (CDH1) repressor SLUG (SNAI2) and the basic helix-loop-helix transcription factor TWIST1 inhibit CDH1 expression in poorly differentiated malignancies as inducers of epithelial-mesenchymal transition. Epithelial-mesenchymal transition has been implicated in progression from well to poorly differentiated/anaplastic thyroid carcinoma but the expression of SNAI2 and TWIST1 proteins and their phenotypic association in human thyroid cancers has not been extensively studied. We examined the expression of SNAI2, TWIST1 and CDH1 by immunohistochemistry in a panel of well-differentiated and anaplastic thyroid cancers and by qRT-PCR in thyroid cell lines. Ten normal thyroids, 33 follicular adenomas, 56 papillary thyroid carcinomas including 28 follicular variants, 27 follicular carcinomas and 10 anaplastic thyroid carcinomas were assembled on a tissue microarray and immunostained for SNAI2, TWIST1 and CDH1. Most (8/10) anaplastic thyroid carcinomas demonstrated strong nuclear immunoreactivity for SNAI2 with associated absence of CDH1 in 6/8 cases (75%). TWIST1 was expressed in 5/10 anaplastic thyroid carcinomas with absence of CDH1 in 3/5 (60%) cases. These findings were confirmed in whole sections of all anaplastic thyroid carcinomas and in a separate validation set of 10 additional anaplastic thyroid carcinomas. All normal thyroids, follicular adenomas, papillary and follicular thyroid carcinomas were negative for SNAI2 and TWIST1 (P<0.0001) and all showed strong diffuse immunoreactivity for CDH1 (P=0.026). Expression of SNAI2, TWIST1 and CDH1 mRNA varied in a normal thyroid, papillary carcinoma and two anaplastic thyroid carcinoma cell lines tested, but the highest levels of CDH1 mRNA were detected in the normal thyroid cell line while the anaplastic thyroid carcinoma cell line demonstrated the highest levels of SNAI2 and TWIST1 mRNA. Our findings support the role of epithelial-mesenchymal transition in the development of anaplastic thyroid carcinoma.

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Conflict of interest statement

Disclosure/conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of SNAI2, TWIST1 and CDH1 immunolabeling in (a) papillary thyroid carcinoma, (b) follicular thyroid carcinoma and (c) anaplastic thyroid carcinoma. Strong diffuse nuclear staining for SNAI2 and TWIST1 is observed in anaplastic thyroid carcinoma accompanied by loss of membranous staining for CDH1. The patient died in less than a month after the diagnosis. Papillary thyroid carcinoma and follicular thyroid carcinoma are positive for CDH1, but negative for SNAI2 and TWIST1.
Figure 2
Figure 2
Expression of SNAI2, TWIST1 and CDH1 mRNA in the normal thyroid, papillary thyroid carcinoma and anaplastic thyroid carcinoma cell lines by qRT-PCR. The highest levels of CDH1 mRNA were detected in the normal thyroid cell line while the T21 anaplastic thyroid carcinoma cell line demonstrated the highest levels of SNAI2 and TWIST1 mRNA.
See this image and copyright information in PMC

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