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 home odomain transcription factors, is a mediator of thyroid-specific transcript ion of the thyroglobulin (TG) gene. The combined immunohistochemical profil e of TTF-1, TG, cy tokeratin 7 (CK7), and cytokeratin 20 (CK20) in neoplasm s of the thyroid gland and their metastases to other sites has not been def ined previously. Formalin-fixed tissue of 43 thyroid tumors, including 31 c arcinomas and 12 adenomas, and 16 metastasic lesions were immunostained usi ng monoclonal antibodies to TTF-1, TG, CK7, and CK20. Immunoreactivity of t he primary tumors (adenomas and carcinomas) for TTF-I was seen in 32 cases (74%), TG 32 (74%), and CK7 34 (79%), whereas none (0%) showed positivity f or 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 differ entiated (6/7), (4/7), and (6/7); oncocytic (Hurthle) cell (2/6), (6/6), an d (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 p ositivity for TTF-I only. Of the six follicular adenomas, five were positiv e for TTF-l, six for TG, and six for CK7. Among the six oncocytic cell aden omas, five were reactive for TTF-1, five for TG, and all six for CK7. Twelv e (75%) of the 16 metastatic tumors were positive for TTF-1, 10 (63%) for T G, 15 (94%) for CK7, and none (0%) for CK20. In summary, TTF-1 and TG are d emonstrable by immunohistochemistry in the majority of thyroid neoplasms. C ompared with TG, an antibody to TTF-1 is a similarly sensitive marker for t hyroid tumors. Moreover, TTF-I is a more sensitive marker for poorly differ entiated carcinomas and metastasis. In most cases, its nuclear pattern of i mmunoreactivity facilitates interpretation. Thyroid tumors are CK7+/CK20-. The panel of antibodies for TG, TTF-1, CK7, and CK20 is useful when the thy roid origin of a metastatic tumor is a consideration.