Comparison of Thyroid Transcription Factor-1 Expression by 2 Monoclonal Antibodies in Pulmonary and Nonpulmonary Primary Tumors

Abstract

Thyroid transcription factor-1 (TTF-1) is a transcription factor that plays a role in the development and physiology of the thyroid and lungs. Expression of TTF-1 is used as a marker of lung and thyroid clinically. Commercially available clones of TTF-1 monoclonal antibodies, 8G7G3/1 and SPT24, have been reported to have different sensitivities for the detection of neoplasms of different origins. Although they are used extensively in daily practice, a comprehensive comparative study of these antibodies in a wide variety of neoplasms is lacking. We examined TTF-1 expression in primary tumors of the lung, prostrate, pancreas, stomach, salivary glands, breast, bladder, colon and squamous cell carcinoma of the head and neck and compared the results obtained with both TTF-1 clones. The SPT24 clone detected more primary lung tumors of all histologic subtypes. Importantly, the SPT24 clone detected a significantly higher number of squamous cell carcinomas and carcinoid tumors of the lung. Among non-pulmonary primary tumors, a significant number of invasive urothelial carcinoma of the bladder (5.1%) was TTF-1 positive. Additionally, a small proportion of prostate (1.2%), stomach (0.9%), salivary gland (1.8%), and colon (2.5%) carcinomas were positive with both clones. Notably, both clones stained the same non-pulmonary tumors with similar intensity and distribution. Carcinomas of the pancreas, breast and squamous cell carcinomas of the head and neck were negative with both clones. In summary, the SPT24 clone detected a higher number of pulmonary non-small cell tumors of all histologic subtypes while both clones stained a similar proportion of non-pulmonary tumors.

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

“…16,17,29 The reason for this reactivity is most likely the use of a lower-specificity TTF-1 antibody (SPT24; NovoCastra) in this study, whereas it was previously shown that a higher-specificity (but lower sensitivity) TTF-1 clone 8G7G3/1 (DAKO) is consistently non-reactive in squamous cell carcinomas positive by SPT24. 30 All squamous cell carcinomas with TTF-1 reactivity in this study were negative for a novel adenocarcinoma marker Napsin A (data not shown) further supporting that this labeling is likely non-specific and is unrelated to glandular differentiation. Although this is a theoretical pitfall for classification of double-positive tumors as adenocarcinoma in laboratories utilizing SPT24 antibody, this is readily resolved by taking into account the ratio of TTF-1/p63 reactivity (low in squamous cell carcinoma vs high in adenocarcinoma) or p63/CK5/6 coexpression in squamous cell carcinoma.…”

Comparative immunohistochemical analysis of pulmonary and thymic neuroendocrine carcinomas using PAX8 and TTF-1

“…In the past, numerous studies have focused on how to separate pulmonary from non-pulmonary neuroendocrine carcinomas, especially those of gastrointestinal or pancreatic origin using immunohistochemical markers. 7,[14][15][16][17][18][19][20][21][22][23] In this scenario, the use of TTF-1 has attracted a lot of attention. TTF-1 is a transcription factor that has been linked with expression in lung and thyroid neoplasms.…”

“…7,[24][25][26] The documented expression of TTF-1 in typical and atypical carcinoids of lung origin has been very variable ranging from 0 to 94% and 0 to 100%, respectively. 7,[14][15][16][17][18][19][20][21][22][23][27][28][29][30][31] This corresponds to an average expression rate of 34.3% for carcinoid tumors and 37.3% for atypical carcinoid tumors. This contrasts with neuroendocrine carcinomas of non-pulmonary origin, the majority which are reportedly negative for this marker, 15,16,18,19,23 although isolated cases of low grade gastrointestinal neuroendocrine carcinoma may show some reactivity with TTF-1.…”

p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma

“…This is an especially important consideration in small specimens, where internal control cells may not be represented and, unlike whole tissue sections, technical failure may not be apparent. Furthermore, it is well documented that TTF-1 (specifically the SPT24 clone) can rarely show focal reactivity in squamous cell carcinomas, 51 further complicating the dependence of p63 interpretation on TTF-1 status. p40 therefore offers a significant advantage over p63 in that its interpretation does not require CK5/6 as additional squamous marker and does not depend on TTF-1.…”