Value of thyroid transcription factor-1 immunostaining in tumor diagnosis: a review and update

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.