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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 9 3228-3234
Copyright © 1999 by The Endocrine Society

Original Studies

Expression of the Na+/I- Symporter Gene in Human Thyroid Tumors: A Comparison Study with Other Thyroid-Specific Genes1

Vladimir Lazar, Jean-Michel Bidart, Bernard Caillou, Cedric Mahé, Ludovic Lacroix, Sebastiano Filetti and Martin Schlumberger

Departments of Clinical Biology (V.L., J.M.B., L.L.), Pathology (B.C.), Biostatistics (C.M.), and Nuclear Medicine (M.S.), Institut Gustave Roussy, 94805 Villejuif, France; and Dipartimento di Medicina Sperimentale e Clinica, Policlinico Mater Domini (S.F.), 88100 Catanzaro, Italy

Address all correspondence and requests for reprints to: Prof. M. Schlumberger, Institut Gustave-Roussy and University Paris-Sud, 39 rue Camille Desmoulins, 94805 Villejuif, France.

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 thyroid carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves’ thyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 normal thyroid tissues were used as reference. A kinetic quantitative PCR method, based on the fluorescent TaqMan methodology and real-time measurement of fluorescence, was used.

NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fold) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in toxic adenomas and Graves’ thyroid tissues (up to 140-fold). TPO expression was 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 some thyroid carcinomas.

In thyroid cancer tissues, a positive relationship was found between the individual levels of expression of NIS, TPO, Tg and TSH-R. No relationship was found with the age of the patient. Higher tumor stages (stages >I vs stage 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, 131I uptake was studied in vivo; NIS expression was low in all samples; 3 patients with normal Glut-1 gene expression had 131I uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I uptake.

In conclusion, this study shows 1) a reduced expression of NIS gene in most hypofunctioning benign and malignant thyroid tumors; 2) a differential regulation of the expression of thyroid-specific genes; 3) an increased expression of Glut-1 gene in some malignant tumors that may suggest a role for glucose derivative tracers to detect in vivo thyroid cancer metastases by positron emission tomography scanning.




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