Thyroid transcription factor-1 in normal, hyperplastic, and neoplastic follicular thyroid cells examined by immunohistochemistry and nonradioactive in situ hybridization.

Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. We examined the expression of TTF-1 in non-neoplastic and neoplastic thyroid tissues. By immunohistochemistry, the nuclei of normal and hyperplastic follicular cells strongly reacted with the antibody against TTF-1. Immunohistochemistry also revealed a distinctive nuclear positivity of TTF-1 in all 33 differentiated follicular cell tumors, including 15 follicular adenomas, 5 follicular carcinomas, and 13 papillary carcinomas. No immunoreactions were observed in three of four undifferentiated carcinomas, whereas an isolated and weak nuclear positivity was obtained in one. In normal and hyperplastic tissues, the distribution of TTF-1 was fairly related to that of thyroid-specific proteins thyroglobulin and thyroperoxidase. However, discrepancies in the distribution were observed in tumor tissues. By in situ hybridization, the riboprobe hybridized distinctively with the cytoplasm of neoplastic cells as well as normal follicular cells. Papillary carcinoma cells expressed TTF-1 mRNA in all but two cases, and its expression was also demonstrated in one of four undifferentiated carcinomas. Reverse transcription-polymerase chain reaction confirmed the presence of TTF-1 mRNA in two human undifferentiated carcinoma cell lines, TTA-1 and TTA-2. In conclusion, the investigation of TTF-1 provides useful information on the functional activities and/or differentiation of thyroid tumors and may lead to an increase in our understanding of the biologic nature of thyroid tumors.