Thyroid transcription factor-1

A homeodomain-containing nuclear transcription protein of the Nkx2 gene family. The commercially available monoclonal antibody 8G7G3/1 can be used on formalin-fixed, paraffin-embedded tissues. The monoclonal antibody probably has greater sensitivity than the polyclonal antibody used in some early studies.

Staining for TTF-1 is nuclear.

Immunohistochemical expression

TTF-1 is expressed in various normal tissues: follicular cells of the thyroid, type II epithelial cells of the alveoli4 and a subset of bronchiolar cells4, the anterior pituitary, parathyroid gland, parafollicular C-cells and in certain regions of the brain.



73% (322/4445, 70/976, 23/2612)

bronchoalveolar carcinoma

86% (25/29)2

small cell carcinoma

90% (170/1855,7,8, 43/529)

squamous cell carcinoma

8% (20/2015, 6/1196, 0/1212)

basaloid squamous cell carcinoma


basaloid carcinoma


large cell carcinoma

26% (16/62)5, 0/26

large cell neuroendocrine carcinoma

2/47, 6/85, 18/4412

typical carcinoid

33% (22/68)5,7, 16/1710

atypical carcinoid

92% (11/12)5,7, 3/310

metastatic pulmonary carcinoid


sclerosing haemangioma

97% (36/37)3

Extra-pulmonary adenocarcinoma (excluding thyroid)

1% (2/286)5

Extra-pulmonary small cell carcinoma (excluding skin)

36% (41/113), various sites

Extra-pulmonary large cell neuroendocrine carcinoma

1/4 (various sites)7

Extra-pulmonary carcinoid

1% (1/207, 0/5010, 0/4911)

Extra-pulmonary endocrine tumours

parathyroid adenoma


pituitary adenoma


pancreatic endocrine tumour




Malignant mesothelioma

0% (0/952, 0/244)



13/155, 5/510

follicular carcinoma

14/145, 5/510

papillary carcinoma

96% (27/285, 5/510)

Hurtle cell carcinoma


Insular carcinoma


medullary carcinoma

15/165,7, 10/1010

anaplastic carcinoma

0/85, 2/510

Thymic neoplasms

0/201, 0/310

Merkel cell carcinoma of skin

0/375,7, 0/239

When large cell neuroendocrine carcinoma of the lung is a component of a combined tumour, it adopts the TTF-1 reactivity of the other component, positive where it is small cell carcinoma and with some adenocarcinomas , negative where it is squamous cell carcinoma12.

Diagnostic utility


positive predictive value

negative predictive value

To differentiated pulmonary from extrapulmonary adenocarcinoma (best used in combination with cytokeratins 7 and 20)



To show tumour is an extra-pulmonary small cell carcinoma, not a Merkel cell carcinoma



 To show carcinoid is of pulmonary origin




1S Pomplun. Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms. Abstract 158, Pathological Society of Great Britain and Ireland January 2001.

2A Khoor et al. Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. Human Pathology 1999;30:695-700.

3M Devousassoux-Shisheboran et al. A clinicopathological study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies. Am J Surg Pathol 2000; 24: 906-916.

4Di Loreto C et al. TTF-1 protein expression in pleural malignant mesotheliomas and adenocarcinomas of the lung. Cancer letters 1998;124:73-78.

5Ordonez NG. Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Advances in Anatomic Pathology 2000; 7(2): 123-127.

6Pelosi G et al. Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung. Am J Surg Pathol 2001;25:363-372.

7Kaufmann 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.

8Ordonez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol 2000;24:1217-1223.

9Cheuk W et al. Immunostaining for thyroid transcription factor-1 and cytokeratin 20 aids in the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinoma. Arch Pathol Lab Med 2001;125:228-231.

10Oliviera AM et al. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neduroendocrine tumors of other sites. Am J Surg Pathol 2001;25:815-819.

11Agoff, S. N., Lamps, L. W., Philip, A. T., Amin, M. B., Schmidt, R. A., True, L. D., Folpe, A. L. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumours. Mod Pathol 2000;13:238-242.

12Sturm, N., Lantuejoul, S., Laverriere, M. H., Papotti, M., Brichon, P. Y., Brambilla, C., Brambilla, E. Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung. Hum Pathol 2001;32:918-925.