Thyroid-specific gene expression in the multi-step process of thyroid carcinogenesis

Thyroid-specific transcription factors TTF-1 and Pax-8 play a decisive role in the determination and maintenance of cellular phenotype activating thyr oglobulin (Tg), thyroperoxidase (TPO), thyrotropin receptor (TSH-R) and the sodium/iodide symporter (NIS) gene transcription. In the present work, we have studied the expression of TTF-1 and Pax-8 and their target genes in sa mples derived from thyroid neoplasms of follicular origin, as well as in me dullary carcinoma (MTC), obtained from surgery or from fine needle aspirati on (FNA) biopsies. The results show that TTF-1 and Pax-8 are expressed in w ell differentiated adenomas and that their expression decreases in less dif ferentiated papillary and folIicular carcinomas and is lost in undifferenti ated anaplastic carcinomas. Parallel levels of Tg, TPO and TSH-R expression were found in the same neoplasm samples. Interestingly TSH-R and TTF-1 gen e expression was found in MTC samples. Furthermore, the expression of the t hyroid-specific genes and their transcription factors is lost in thyroid ce lls derived from follicular, papillary and anaplastic human carcinomas. In these cells, Tg, TPO and TSH-R promoter activities were absent. Cotransfect ion with expression vectors for TTF-1 and Pax-8 resulted in the stimulation of transcription to a different extent for each promoter. These results ma y be clinically relevant for the evaluation and prognosis of thyroid cancer since the loss of specific markers correlates with the degree of tumor dif ferentiation. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris.