TTF-1 [SPT24]

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Thyroid transcription factor-1 (TTF-1) is a 38 kDa member of the NKX2 family of homeodomain transcription factors. TTF-1 is mostly detected in primary lung adenocarcinomas and small cell carcinomas (1). TTF-1 can be very useful in lung cancers when used in a panel with Desmoglein 3, p40 and Napsin A antibodies (2-3).

Commercially available thyroid transcription factor-1 (TTF-1) monoclonal antibodies 8G7G3/1 and SPT24 have been shown to have different sensitivities in lung adenocarcinomas (LADC) and lung squamous cell carcinomas (SqCC) (4-6). A study by Masai, et al. demonstrated that SPT24 was much more sensitive than 8G7G3/1 in LADC (72.4% and 65.4% respectively). However, the study demonstrated that SPT24 stained a higher percentage of lung SqCC (16.8% vs. 1%). Higher sensitivity of SPT24 in lung SqCC has also been shown to be heavily influenced by different detection systems (4-5).

Higher sensitivity for LADC versus lung SqCC can be achieved with SPT24, compared to 8G7G3/1, while retaining specificity, by the use of a cut-off value and optimal antibody titer. In an in-house study, SPT24 was titered to achieve negative staining in normal liver (no cytoplasmic staining observed). A cut-off value of ≥10% of tumor cells positive for TTF-1 with a staining intensity of ≥ 1+ was used to identify TTF-1 positive cases. Using this approach, SPT24 was highly sensitive for LADC (53/60, 88%), compared to 8G7G3/1 (38/60, 63%), with equivalent specificity for both clones versus lung SqCC (2/137, 1.5%).

Use of lung SqCC specific markers, such as Desmoglein 3 and p40, may identify TTF-1 positive cases of squamous cell origin. Additionally, the use of Napsin A may confirm lung adenocarcinoma as the co-expression of Napsin A and TTF-1 in lung cancers has been shown to be more pulmonary specific than either one used alone (7). Finally, unlike clone 8G7G3/1, no cytoplasmic staining in lung cancers has been observed with clone SPT24 (8).

Intended Use

IVD

Format

Concentrate, ONCORE, Predilute

Volume

0.1 ml, 1.0 ml, 6.0 ml, 60 Tests

Source

Mouse Monoclonal

Clone

SPT24

Isotype

IgG1/kappa

Antigen

TTF-1

Localization

Nuclear

Positive Control

Lung adenocarcinoma

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1. Di Loreto C, et al. Immunocytochemical expression of tissue specific transcription factor-1 in lung carcinoma. J Clin Pathol. 1997 Jan; 50(1):30-2.
2. Tacha D, et al. A 6-antibody panel for the classification of lung adenocarcinoma versus squamous cell carcinoma. Appl Immunohistochem Mol Morphol. 2012 May; 20 (3):201-7.
3. Brown AF, et al. Tissue-preserving antibody cocktails to differentiate primary squamous cell carcinoma, adenocarcinoma, and small cell carcinoma of lung. Arch Pathol Lab Med. 2013 Sep; 137(9):1274-81.
4. Masai K, et al. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol. 2013 Jul; 21(4):292-7.
5. Matoso A, et al. Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors. Appl Immunohistochem Mol Morphol. 2010 Mar; 18(2):142-9.
6. Ordóñez NG. Value of thyroid transcription factor-1 immunostaining in tumor diagnosis: a review and update. Appl Immunohistochem Mol Morphol. 2012 Oct; 20 (5):429-44.