title: Nuclear localization of thyroid transcription factor-1 correlates with serum thyrotropin activity and may be increased in differentiated thyroid carcinomas with aggressive clinical course.
abstract: Thyroid transcription factor 1 (TTF-1) is essential for thyroid differentiation and regulates expression of thyroglobulin, thyroid peroxidase, sodium/iodide symporter, and thyrotropin receptor (TSH-R) genes. Because thyrotropin (TSH) upregulates these same genes, we hypothesized TSH-R activation might increase TTF-1 and that TTF-1 might be differentially expressed in benign and malignant thyroid disease. TTF-1 expression and sub-cellular localization were determined by immunohistochemistry in 62 thyroid carcinomas, 15 benign lesions, and 2 normal thyroids. Nuclear TTF-1 was detected in benign (77%) and malignant lesions (69%), with similar intensity in both (1.1+/-0.19 versus 1.0+/-0.10). Nuclear TTF-1 staining correlated with the effective serum TSH level (p = 0.02) and patient age (p < 0.05). Nuclear TTF-1 was detected in 35 papillary thyroid carcinomas (PTC), of which 23% developed recurrent or persistent disease, and was absent from 18 PTC, of which only 6% recurred (p = 0.06). We conclude that nuclear TTF-1 correlates with serum TSH activity, increases with age, and may be increased in persistent or recurrent PTC.
authors.affiliation: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Fenton
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: H B
authors.initials: HB
authors.lastname: Burch
authors.forename: R M
authors.initials: RM
authors.lastname: Tuttle
authors.forename: G L
authors.initials: GL
authors.lastname: Francis
mesh_terms: D000293:Adolescent; D000328:Adult; D002467:Cell Nucleus / Q000737:chemistry*; D002648:Child; D018450:Disease Progression; D005260:Female; D006042:Goiter / Q000378:metabolism / Q000473:pathology; D006111:Graves Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis* / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D016606:Thyroid Nodule / Q000378:metabolism / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000097:blood*; D014157:Transcription Factors / Q000032:analysis* / Q000096:biosynthesis
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013972:Thyrotropin