Thyroid transcription factor

Pan CC, Chen PC, Tsay SH, et al. Cytoplasmic immunoreactivity for thyroid transcription factor-1 in hepatocellular carcinoma a comparative immunohistochemical analysis of four commercial antibodies using a tissue array technique. Am. J. Clin. Pathol. 2004 121 343-349. 

Liu J, Farhood A. Immunostaining for thyroid transcription factor-1 on fine-needle aspiration specimens of lung tumors a comparison of direct smears and cell block preparations. Cancer 2004 102 109-114. 

Zhang L, Whitsett JA, Stripp BR (1997) Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1. Biochim Biophys Acta 1350(3) 359-367... 

FIGURE 1.31 Section of normal lung tissue stained with TTF-1 (thyroid transcription factor), exhibiting specific nuclear positivity of the alveolar lining cells (pneumocytes). 

Determine if there is expression of cell-specific products, cell-specific structures, and transcription factors or receptors that are unique identifiers of cell types (e.g., neuroendocrine granules, peptide hormones, thyroglobulin, PSA, prostate-specific membrane antigen, inhibin, gross cystic disease fluid protein [GCDEP], villin, uroplakin, thyroid transcription factor-1 [TTE-1] or transcription factor CDX-2). 

Thyroid transcription factor-1 (TTF-1), a nuclear tissue-specific protein transcription factor, is found in thyroid and thyroid tumors regardless of histologic type (except anaplastic type), as well as in lung carcinomas including adenocarcinomas (75%), non-small cell carcinomas (63%), neuroendocrine and small cell carcinomas (>90%), and squamous cell carcinomas (10%).258-258 Selectively expressed during embryogenesis in the thyroid, the diencephalon of the brain, and in respiratory epithelium, TTF-1 binds to and activates factors for surfactant protein derived from Clara cells.255 TTF-1 is rarely seen in carcinomas outside of the lung or thyroid... 

FIGURE 8.13 Thyroid transcription factor 1 (TTF-1) antibody identifies 60% to 70% of pulmonary adenocarcinomas (A, B) and 95% of pulmonary small cell carcinomas (C, D). 

Goldstein NS, Thomas M. Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies. Am Clin Pathol. 2001 116 319-325. 

Lau SK, Desrochers MJ, Luthringer DJ. Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas an immunohistochemical evaluation of 67 cases. Mod Pathol. 2002 15 538-542. 

Bejarano PA, Baughman RP, Biddinger PW, et al. Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod Pathol. 1996 9 445-452. 

Stahlman MT, Gray ME, Whitsett JA. Expression of thyroid transcription factor-l(TTF-l) in fetal and neonatal human lung. J Histochem Cytochem. 1996 44 673-678. 

Folpe AL, Gown AM, Lamps LW, et al. Thyroid transcription factor-1 immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol. 1999 12 5-8. 

Holzinger A, Dingle S, Bejarano PA, et al. Monoclonal antibody to thyroid transcription factor-1 production, characterization, and usefulness in tumor diagnosis. Hybridoma. 1996 15 49-53. 

Khoor A, Whitsett JA, Stahlman MT, et al. Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. Hum Pathol. 1999 30 695-700. 

Kaufmann O, Dietel M. Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites. Histopathology. 2000 36 415-420. 

Ordonez NG. Value of thyroid transcription factor-1 im-munostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol. 2000 24 1217-1223. 

Afify AM, al-Khafaji BM. Diagnostic utility of thyroid transcription factor-1 expression in adenocarcinomas presenting in serous fluids. Acta Cytol. 2002 46 675-678. 

Jang KY, Kang MJ, Lee DG, Ghung MJ. Utility of thyroid transcription factor-1 and cytokeratin 7 and 20 immunostaining in the identification of origin in malignant effusions. Anal Quant Cytol Histol. 2001 23 400-404. 

Roh MS, Hong SH. Utility of thyroid transcription factor-1 and cytokeratin 20 in identifying the origin of metastatic carcinomas of cervical lymph nodes. / Korean Med Set. 2002 17 512-517. 

Chang YL, Lee YC, Liao WY, Wu GT. The utility and limitation of thyroid transcription factor-1 protein in primary and metastatic pulmonary neoplasms. Lung Cancer. 2004 44 149-157. 

Wieezorek TJ, Pinkus JL, Glickman JN, Pinkus GS. Gompari-son of thyroid transcription factor-1 and hepatocyte antigen immunohistochemical analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma. Am J Clin Pathol. 2002 118 911-921. 

Siami K, McCluggage WG, Ordonez NG, et al. Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am Surg Pathol. 2007 31 1759-1763. 

Bejarano PA, Nikiforov YE, Swenson ES, Biddinger PW. Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms. Appl Immunohistochem MolMorphol. 2000 8 189-194. 

Nonaka D, Tang Y, Chiriboga L, et al. Diagnostic utility of thyroid transcription factors Pax8 and TTE-2 (EoxEl) in thyroid epithelial neoplasms. Mod Pathol. 2008 21 192-200. 

Neuroendocrine carcinomas and small cell neuroendocrine carcinomas are almost invariably positive for cytokeratins (such as CAM 5.2 and AE 1/3), synaptophysin, chromogranin, and neuron-specific enolase. A dotlike pattern of positivity may be seen in cytokeratin stains. They are negative for cytokera-tin 20, S-100, and neurofilament.About half of small cell neuroendocrine carcinomas are positive for thyroid transcription factor (TTF-1) and at least one... 

The differential diagnosis of carcinoid and atypical carcinoid tumors of the larynx includes paraganglioma, melanoma, and medullary thyroid carcinoma. Paragangliomas are rarely always negative for cyto-keratins and also exhibit the characteristic susten-tacular cell pattern with SlOO protein. Thyroid transcription factor-1 (TTEl) is positive in medullary thyroid carcinoma, as are calcitonin and CEA. Melanomas will typically stain with HMB45 and tyrosinase, both of which are negative in neuroendocrine carcinomas. 

Rare cases of lung carcinoma can metastasize to the head and neck, particularly to the low cervical lymph nodes. These tumors usually carry the same immunophenotype as the primary lung tumor. Typical stains that are used to aid in this differential diagnosis will include cytokeratin 7, cytokeratin 20, and thyroid transcription factor-1 (TTF-1). 

Cheuk W, Kwan MY, Suster S, et al. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch Pathol Lab Med. 2001 125(2) 228-231. 

Oliveira AM, Tazelaar HD, Myers JL, et al. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol. 2001 25(6) 815-819. 

FIGURE 10.9 Well-differentiated follicular thyroid carcinoma. Im-munoperoxidase stain for thyroid transcription factor-1 shows the typical nuclear positivity. 

Thyroid transcription factor-2 (TTF-2) and PAX-8, which are essential for thyroid organogenesis and differentiation, have also been studied in thyroid tumors. TTF-1, TTF-2, and PAX-8 were expressed in differentiated and poorly differentiated thyroid carcinomas, whereas TTF-1 and TTF-2 were expressed in 18% and 7% of anaplastic carcinomas, respectively. PAX-8, on the other hand, was present in 79% of anaplastic carcinomas. TTF-2 was negative in all other neoplastic and non-neoplastic tissues including those of pulmonary origin. Although PAX-8 was present in a variety... 

The t(2 3)(ql3 p25) translocation, found in a subset of thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX-8 to domains A-F of the peroxisome proliferation-activated receptor (PPAR) y 1 (Hg. 10.13). Studies using PCR and immunohistochemistry demonstrated that most follicular carcinomas positive for PPAR Y were widely invasive while tumors lacking the rearrangement were PPAR y negative. Papillary carcinomas and Hurthle cell tumors were negative. Other studies, however, have reported positivity both in follicular carcinomas and adenomas. 

FIGURE 10.25 Distribution of markers in parathyroid adenomas. KER(PAN), pancytokeratin PTH, parathyroid hormone CHR-A, chromogranin A BCL-2 PSA, prostatic specific antigen cyclin D1 TTF-1, thyroid transcription factor-1 TGB, thyroglobulin. 

TTF-1, thyroid transcription factor-1 CK, cytokeratin ER, estrogen receptor, PR, progesterone receptor PSA, prostate-specific antigen PAP, prostatic acid phosphatase. 

Katoh R, Kawaoi A, Miyagi E, et al. Thyroid transcription factor I in normal, hyperplastic and neoplastic thyroid follicular thyroid cells examined by immunohistochemistry and non-ra-dioactive in situ hybridization. Mod Pathol. 2000 13 570-576. Lau SK, Luthringer DJ, Eisen RN. Thyroid transcription fac-tor-I A review. Appl Immunohistochem Mol Morphol. 2002 10 97-102. 

Ordonez NG. Thyroid transcription factor I is a marker of lung and thyroid carcinomas. Adv Anat Pathol. 2000 7 123-127. Kaufmann O, Dietel M. Thyroid transcription factor-I is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B. Histopathology. 2000 36 8-16. 

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