EXPRESSION OF THYROTROPIN RECEPTOR (TSH-R), THYROGLOBULIN, THYROPEROXIDASE, AND CALCITONIN MESSENGER RIBONUCLEIC-ACIDS IN THYROID CARCINOMAS - EVIDENCE OF TSH-R GENE TRANSCRIPT IN MEDULLARY HISTOTYPE

We studied the expression of the TSH receptor (TSH-R), thyroglobulin ( Tg), thyroperoxidase (TPO), and calcitonin (CT) genes in a total of 53 tissues from 30 patients with thyroid carcinoma and from 9 patients w ith benign thyroid diseases. By Northern blot analysis of total RNA pr eparations, CT mRNA was expressed in all cases (n = 6) of medullary th yroid carcinoma (MTC). Surprisingly, 3 of them expressed the TSH-R mRN A, in association with the Tg and TPO mRNAs in 1. The presence of the TSH-R transcript in the neoplastic C-cells was confirmed in 1 MTC by i n situ hybridization using a mixture of 3 oligonucleotide probes deriv ed from dog TSH-R cDNA. With various degrees of expression, all differ entiated thyroid carcinomas (20 papillary and 2 follicular) expressed TSH-R, Tg, and TPO, but not CT mRNAs. On the contrary, samples from 2 patients with anaplastic carcinoma did not express TSH-R, Tg, or TPO m RNA, but 1 of them expressed CT mRNA. All of the transcripts obtained from thyroid carcinomas (both primary and metastatic) were of the same size as the transcripts from normal or benign thyroid tissues, with t he exception of 2 cases of differentiated thyroid cancer, in which TSH -R mRNA of lower mol wt (similar to 4.0 kilobases) was found in the ab sence of alteration in cDNA size and restriction map. The main conclus ions of our study are that 1) the TSH-R gene is expressed in some MTC, which supports, at molecular level, the hypothesis of the existence o f mixed follicular-medullary thyroid tumors; and 2) the expression of TSH-R, Tg, and TPO in undifferentiated thyroid cancer is lost.