Expression of the Na+/I- symporter gene in human thyroid tumors: A comparison study with other thyroid-specific genes

The expression of 4 thyroid tissue-specific genes [Na+/I- symporter (NIS), thyroid peroxidase (TPO), thyroglobulin (Tg), TSH receptor (TSH-R)] as well as of the glucose transporter type 1 (Glut1) gene was analyzed in 90 human thyroid tissues. Messenger ribonucleic acids were extracted from 43 thyroi d carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves' t hyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 nor mal thyroid tissues were used as reference. A kinetic quantitative PCR meth od, based on the fluorescent TaqMan methodology and real-time measurement o f fluorescence, was used. NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fo ld) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in tox ic adenomas and Graves' thyroid tissues (up to 140-fold). TPO expression wa s decreased in thyroid carcinomas, but was normal in cold adenomas; it was increased in toxic adenomas and Graves' thyroid tissues. Tg expression was decreased in thyroid carcinomas, but was normal in the other tissues. TSH-R expression was normal in most tissues studied and was decreased in only so me thyroid carcinomas. In thyroid cancer tissues, a positive relationship was found between the in dividual levels of expression of NIS, TPO, Tg and TSH-R. No relationship wa s found with the age of the patient. Higher tumor stages (stages >I vs stag e I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0 .01). Expression of the Glut1 gene was increased in 1 of 24 adenomas and in 8 of 43 thyroid carcinomas. In 6 thyroid carcinoma patients, I-131 uptake was st udied in vivo; NIS expression was low in all samples; 3 patients with norma l Glut-1 gene expression had I-131 uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I upt ake. In conclusion, this study shows 1) a reduced expression of NIS gene in most hypofunctioning benign and malignant thyroid tumors; 2) a differential reg ulation of the expression of thyroid-specific genes; 3) an increased expres sion of Glut-1 gene in some malignant tumors that may suggest a role for gl ucose derivative tracers to detect in vivo thyroid cancer metastases by pos itron emission tomography scanning.