Value of Thyroid Transcription Factor-1 Immunostaining in Tumor Diagnosis

Abstract

Thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that plays a critical role in the normal development of embryonic epithelial cells of the thyroid and lung. Because TTF-1 expression is highly restricted to epithelial tumors arising in these organs, it is, at present, one of the immunohistochemical markers most commonly used to assist in the differential diagnosis of carcinomas of the lung and thyroid. Recent studies, however, have reported that TTF-1 is not as specific for lung and thyroid carcinomas as was previously thought as it can be found to be expressed, although much less frequently, in some carcinomas arising in other organs, such as the ovaries, endometrium, colon, and breast, as well as in some tumors of the central nervous system. Even though this unexpected TTF-1 positivity has been reported more frequently with the recently available SPT24 anti-TTF-1 monoclonal antibody, it has also been shown to occur with the commonly used 8G7G3/1 clone, albeit in a lower percentage of cases. Despite these findings, TTF-1 remains a very useful immunohistochemical marker in diagnostic pathology.

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

“…TTF1 is expressed in approximately 75% to 80% of lung ADCs, including nonmucinous bronchioloalveolar carcinomas and signet ring cell type and goblet cell type of primary lung ADCs. 15 In lung, TTF1 was reported 15 to stain positively in 30% of sarcomatoid carcinomas, 40% of large cell carcinomas, 24% of mucinous bronchioloalveolar carcinomas, and 5% of SCCs and to be negative in basaloid SCCs. 15 However, in our experience and that of others, TTF1 (clone 8G7G3/1) was not expressed in pulmonary SCCs.…”

“…14 Expression of TTF1 has been reported 15 in pulmonary carcinoid, atypical carcinoid, large cell neuroendocrine carcinomas, and small cell carcinomas in approximately 35%, 50%, 47%, and 90%, respectively. Nearly 100% of thyroid carcinomas, including papillary carcinomas, follicular carcinomas, insular carcinomas, and medullary carcinomas, are positive for TTF1.…”

“…In contrast, in our experience, anaplastic thyroid carcinoma tends to be negative. Based on the Ordonez review article, 15 only 13.7% of anaplastic thyroid carcinomas and 33% of Hürthle cell carcinomas were positive for TTF1. TTF1is not entirely specific for lung or thyroid origins.…”

“…TTF1.-TTF1 is a homeodomain-containing nuclear transcription protein of the NK2 homeobox (NKX2) gene family, which plays a crucial role in organogenesis of the thyroid gland and lung as well as the development of the pituitary gland and the ventral brain. 15 Two commonly used monoclonal antibodies are used in routine practice: clones 8G7G3/1 and SPT24. SPT24 is slightly more sensitive than 8G7G3/1, but its specificity for thyroid and lung ADC appears to be slightly lower.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…15,98 TTF-1 is a nuclear protein involved in the organogenesis of the lung and thyroid, and is expressed in approximately 75% of lung adenocarcinomas. 99 However, it is also highly sensitive and specific for thyroid carcinomas, with the exception of anaplastic carcinoma and a small proportion of other extrapulmonary adenocarcinomas (including ovarian serous carcinomas, endometrial and endocervical adenocarcinomas, and colonic adenocarcinomas). 99,100 Napsin A is predominantly expressed in the lung and kidney, and demonstrates granular and cytoplasmic staining.…”