Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors

Thyroid transcription factor-1 (TTF-1), a nuclear transcription protein selectively expressed in the thyroid, the diencephalon, and respiratory epithelium, is expressed in more than 90% of pulmonary small cell carcinomas (SCLCs) and in almost 75% of pulmonary non-small cell carcinomas (NSCLCs), but it is absent in typical pulmonary carcinoids (TCs). Therefore, it was thought that SCLC and NSCLC might share a common lineage, different from that of TC. TTF-1 expression in atypical pulmonary carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNECs) was not studied previously. We examined TTF-1 expression in 51 TCs, 9 ACs, 8 LCNECs, and 21 SCLCs with use of formalin-fixed material and heat-induced epitope retrieval. TTF-1 expression was seen in 18 (35%) of 51 TCs, all of the 9 ACs, 6 (75%) of the 8 LCNECs, and 20 (95%) of the 21 SCLCs. These results reinforce earlier findings of the excellent sensitivity of TTF-1 for SCLC, and they show similar sensitivity for AC and LCNEC, but they argue against the hypothesis that SCLC and TC are of different cell lineages. The ubiquity of TTF-1 expression in pulmonary NECs demonstrated in this study also argues against its use in their subclassification.