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 trans criptional activity of thyroid-specific genes. We examined the expression o f TTF-1 in non-neoplastic and neoplastic thyroid tissues. By immunohistoche mistry, the nuclei of normal and hyperplastic follicular cells strongly rea cted 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, an d 13 papillary carcinomas. No immunoreactions were observed in three of fou r undifferentiated carcinomas, whereas an isolated and weak nuclear positiv ity was obtained in one, in normal and hyperplastic tissues, the distributi on of TTF-1 was fairly related to that of thyroid-specific proteins thyrogl obulin and thyroperoxidase. However, discrepancies in the distribution were observed in tumor tissues. By irt situ hybridization, the riboprobe hybrid ized distinctively with the cytoplasm of neoplastic cells as well as normal follicular cells. Papillary carcinoma cells expressed TTF-1 mRNA in all bu t two cases, and Its expression was also demonstrated ha one of four undiff erentiated carcinomas. Reverse transcription-polymerase chain reaction conf irmed the presence of TTF-1 mRNA in two human undifferentiated carcinoma ce ll lines, TTA-1 and TTA-2. in conclusion, the investigation of TTF-1 provid es useful information on the functional activities and/or differentiation o f thyroid tumors and may lead to an increase in our understanding of the bi ologic nature of thyroid tumors.