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.

Expression of the Sodium Iodide Symporter and Thyroglobulin Genes Are Reduced in Papillary Thyroid Cancer

“…However, the paired analysis clearly demonstrated a significant decrease in TG expression in thyroid cancers compared with corresponding normal thyroid tissue (759 Ϯ 245 pg Eq vs. 1854 Ϯ 542 pg Eq, P ϭ .03). These findings are consistent with those reported by quantitative RT-PCR, qualitative RT-PCR, and immunohistochemical analysis (23)(24)(25)(26).…”

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

“…Northern blot analysis of tpo mRNA in carcinoma has yielded discrepant results (Hoang-Vu et al 1992, Elisei et al 1994 and the hypothesis that an immunological alteration accounts for the variable affinity of TPO for different antibodies (Mizukami et al 1994, Tanaka et al 1996 has been questioned (Czarnocka et al 2001). In pilot studies using immunohistochemistry and in situ hybridization, we observed more heterogeneity in TPO and tpo mRNA in malignant tumors (De Micco et al 2000).…”

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

“…Interest in NIS has, therefore, risen with regard to the possibility of using it in the treatment and diagnosis of breast cancer [5,6]. However, thyroid tumors gradually lose the expression of differentiation genes, including NIS, during the dedifferentiation process [7].…”