Molecular and pathologic study on functional and regulation of thyroid tumors

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Thyroid transcription factor-1 (TTF-1), as recognized in 1990, is a thyroid specific transcription factor that is a homeodomain-containing protein responsible for transcriptional activation of thyroid-specific genes, thyroglobuline, thyroperoxidase, and thyrotropin receptor. The structure and function of TTF-1 have been investigated by several authors. However, little is known about the expression in diseased thyroid tissues.We investigated the expression of thyroid transcription factor-1 (TTF-1) using immunohistochemistry and demonstrated the nuclear localization of TTF-1 in normal follicular cells and follicular cell derived benign and malignant thyroid tumors. However, we failed to demonstrate TTF-1 in undifferentiated carcinoma cells. In situ hybridization for TTF-1mRNA supported the immunohistochemical results. Molecular methods, Northern blotting and RT-PCR analyses, revealed that expression of TTF-1mRNA was demonstrated not only in normal thyroid tissues but also in various histologic types of thyroid tumors.Interestingly, TTF-1 expression was evident in normal parafollicular cells (C cells) and medullary thyroid carcinomas derived from C cell. Immunohistochemistry for TTF-1 and in situ hybridization for TTF-1 mRNA supported these results.From our results, TTF-1 plays important roles in hormonogenetic mechanism in thyroid follicular cells and C cells and molecular examinations in conjunction with pathologic examinations for this transcriptional factor can be useful in understanding of physiological nature of thyroid tumors and in pathologic diagnosis of thyroid diseases.