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.

Abstract

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 with benign thyroid diseases. By Northern blot analysis of total RNA preparations, CT mRNA was expressed in all cases (n = 6) of medullary thyroid carcinoma (MTC). Surprisingly, 3 of them expressed the TSH-R mRNA, 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 in situ hybridization using a mixture of 3 oligonucleotide probes derived from dog TSH-R cDNA. With various degrees of expression, all differentiated 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 mRNA, 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 the exception of 2 cases of differentiated thyroid cancer, in which TSH-R mRNA of lower mol wt (approximately 4.0 kilobases) was found in the absence of alteration in cDNA size and restriction map. The main conclusions 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 of mixed follicular-medullary thyroid tumors; and 2) the expression of TSH-R, Tg, and TPO in undifferentiated thyroid cancer is lost.