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.

Lung	adenocarcinoma	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	0/2812
	basaloid carcinoma	0/2812
	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	8/1810
	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	0/1010
	pituitary adenoma	0/2010
	pancreatic endocrine tumour	0/1010
	phaeochromocytoma	0/510
Malignant mesothelioma		0% (0/952, 0/244)
Thyroid	adenoma	13/155, 5/510
	follicular carcinoma	14/145, 5/510
	papillary carcinoma	96% (27/285, 5/510)
	Hurtle cell carcinoma	1/55
	Insular carcinoma	5/55
	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)	99%	70%
To show tumour is an extra-pulmonary small cell carcinoma, not a Merkel cell carcinoma	100%	76%
To show carcinoid is of pulmonary origin	97%	30%

Differentiation of adenocarcinoma from mesothelioma

If a small cell carcinoma is negative for TTF-1, it is less likely to be of pulmonary origin, but positivity for TTF-1 does not demonstrate that it is on pulmonary origin.

References

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.