Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms.
Thyroid transcription factor-1 (TTF-1), a member of the NKx2 family of homeodomain transcription factors, is a mediator of thyroid-specific transcription of the thyroglobulin (TG) gene. The combined immunohistochemical profile of TTF-1, TG, cytokeratin 7 (CK7), and cytokeratin 20 (CK20) in neoplasms of the thyroid gland and their metastases to other sites has not been defined previously. Formalin-fixed tissue of 43 thyroid tumors, including 31 carcinomas and 12 adenomas, and 16 metastasic lesions were immunostained using monoclonal antibodies to TTF-1, TG, CK7, and CK20. Immunoreactivity of the primary tumors (adenomas and carcinomas) for TTF-1 was seen in 32 cases (74%), TG 32 (74%), and CK7 34 (79%), whereas none (0%) showed positivity for CK20. The distribution of reactivity in the 31 carcinomas for TTF-1, TG, and CK7, respectively was papillary (8/8), (8/8), and (8/8); poorly differentiated (6/7), (4/7), and (6/7); oncocytic (Hürthle) cell (2/6), (6/6), and (4/6); follicular (4/4), (3/4), and (3/4); medullary (1/2), (0/2), and (1/2). One of four anaplastic carcinomas was focally immunoreactive showing positivity for TTF-1 only. Of the six follicular adenomas, five were positive for TTF-1, six for TG, and six for CK7. Among the six oncocytic cell adenomas, five were reactive for TTF-1, five for TG, and all six for CK7. Twelve (75%) of the 16 metastatic tumors were positive for TTF-1, 10 (63%) for TG, 15 (94%) for CK7, and none (0%) for CK20. In summary, TTF-1 and TG are demonstrable by immunohistochemistry in the majority of thyroid neoplasms. Compared with TG, an antibody to TTF-I is a similarly sensitive marker for thyroid tumors. Moreover, TTF-1 is a more sensitive marker for poorly differentiated carcinomas and metastasis. In most cases, its nuclear pattern of immunoreactivity facilitates interpretation. Thyroid tumors are CK7+/CK20-. The panel of antibodies for TG, TTF-1, CK7, and CK20 is useful when the thyroid origin of a metastatic tumor is a consideration.
Bejarano
P A
PA
Department of Pathology, University of Miami School of Medicine, Florida 33136, USA. pbejaran@med.miami.edu
Nikiforov
Y E
YE
Swenson
E S
ES
Biddinger
P W
PW
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D013954:Thyroglobulin / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000096:biosynthesis*
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D007633:Keratins; D013954:Thyroglobulin