Expression of Epithelial-Mesenchymal Transition Regulators Slug and Twist in Thyroid Carcinomas
Darya Buehler, Heather Hardin, Weihua Shan, William Rehrauer, Herb Chen, Ricardo V Lloyd. University of Wisconsin School of Medicine and Public Health, Madison, WI
Background: Epithelial-mesenchymal transition (EMT) has been recognized as an important mechanism of epithelial tumor progression, local invasion and metastasis. The E-cadherin repressor Slug and the basic helix-loop-helix transcription factor Twist inhibit E-cadherin expression in poorly differentiated malignancies as inducers of EMT. Very little is known about the expression of EMT regulators in thyroid cancer. In this study, we examined the expression of Twist, Slug and E-cadherin in a panel of well-differentiated and anaplastic thyroid carcinomas by immunohistochemistry and by RT-PCR in thyroid cell lines.
Design: 10 anaplastic thyroid carcinomas (ATC), 28 follicular carcinomas, 56 papillary thyroid carcinomas (PTC) including 28 follicular variants, 33 follicular adenomas and 10 normal thyroids (NT) were assembled on a tissue microarray using triplicate 0.6 mm cores and examined for expression of E-cadherin, Slug and Twist by immunohistochemistry. Unequivocal nuclear staining for Slug and Twist and membranous staining for E-cadherin were considered for interpretation. Immunoreactivity was scored based on the percentage of cells stained and the intensity of staining. Focal or diffuse moderate or strong staining was considered to be positive. The expression of E-cadherin, Slug and Twist mRNA was tested in various thyroid cell lines including 2 NT, two PTC and 3 ATC.
Results: Most (8/10) ATCs showed strong nuclear immunoreactivity for Slug (6 cases diffuse, 2 cases focal). In five cases (62.5%), Slug expression was associated with absence of E-cadherin. None of the NTs, follicular adenomas, and follicular or papillary carcinomas were immunoreactive for Slug (p<0.0001). All cases of NTs, adenomas and well-differentiated thyroid carcinomas were positive for E-cadherin. Twist was expressed in 5/10 ATCs, but not in NTs, adenomas or well-differentiated carcinomas (p<0.001). By RT-PCR, E-cadherin was expressed in the NT and PTC cell lines only, while Slug and Twist were expressed in both the PTC and ATC cell lines.
Conclusions: The EMT regulators Slug and Twist are expressed in anaplastic thyroid carcinomas and are associated with absence of E-cadherin supporting the role of EMT in this cancer. E-cadherin expression was present in all normal thyroids, follicular adenomas and well-differentiated carcinomas and none of these lesions expressed Slug or Twist. Expression of the EMT marker mRNAs was more complex in cell lines. Immunohistochemical detection of Slug and Twist may be helpful in diagnostically challenging cases of thyroid tumors in limited biopsy samples.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 18, Tuesday Afternoon