Expression of thyroid transcription factor-1 (TTF-1) in human C cells and medullary thyroid carcinomas

Thyroid transcription factor-1 (TTF-1) has been known to regulate the trans criptional activity of thyroid-specific genes in thyroid follicular cells. We recently identified TTF-1 mRNA expression in rat thyroid C cells. The cu rrent study was undertaken to elucidate how TTF-1 is expressed in human C c ells and medullary thyroid carcinomas (MTCs), and how this expression influ ences the functions and clinical behavior of these cells. By immunohistoche mistry, the nuclei of normal and hyperplastic C cells distinctively reacted with antibody against TTF-1, whereas the immunostaining intensity in C cel ls was rather weak and heterogeneous in comparison with that in follicular cells. Identical TTF-1 immunoreactivity was observed in all 15 MTC specimen s examined. The reaction intensity did not depend on tumor patterns or cell features. In nonisotopic in situ hybridization, an antisense riboprobe cle arly hybridized the cytoplasms of C cells and MTC cells, which concurrently showed immunohistochemical positivity for calcitonin. Northern blot analys is indicated a marked hybridization with TTF-1 mRNA of approximately 2.3 kb in an MTC specimen. Furthermore, the presence of TTF-1 mRNA was confirmed by reverse transcription polymerase chain reaction (RT-PCR) in the human MT C cell line, TT, Our results suggest that human thyroid C cells and MTC cel ls express TTF-1 in connection with their functional ability. Therefore, TT F-1 expression can be a functional marker not only for follicular cells and follicular cell tumors but also for C cells and medullary C cell carcinoma s. Copyright (C) 2000 by W.B. Saunders Company.