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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 10 4977-4983
Copyright © 2003 by The Endocrine Society

Correlation between the Loss of Thyroglobulin Iodination and the Expression of Thyroid-Specific Proteins Involved in Iodine Metabolism in Thyroid Carcinomas

A.-C. Gérard, C. Daumerie, C. Mestdagh, S. Gohy, C. de Burbure, S. Costagliola, F. Miot, M.-C. Nollevaux, J.-F. Denef, J. Rahier, B. Franc, J. J. M. De Vijlder, I. M. Colin and M.-C. Many

Histology (A.-C.G., C.M., S.G., C.d.B., J.-F.D., I.M.C., M.-C.M.), Endocrinology (C.D.), and Pathology Units (M.-C.N., J.R.), Université Catholique de Louvain Medical School, and Institut de Recherche Interdisciplinaire, Université Libre de Bruxelles (S.C., F.M.), B-1070 Brussels, Belgium; Service d’Anatomie et de Cytologie Pathologiques, Hôpital Ambroise Paré (B.F.), F-912100 Boulogne, France; and Academic Medical Center, University of Amsterdam (J.J.M.D.V.), NL-1012 Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. M.-C. Many, Histology Unit, Université Catholique de Louvain, Medical School, UCL-5229, 52 avenue Mounier, B-1200 Brussels, Belgium. E-mail: many{at}isto.ucl.ac.be.

Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na+/I- symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H2O2-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T4-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T4-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H2O2-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T4-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.

A.-C.G. is the recipient of FSR grant from Université Catholique de Louvain.

Part of this work was presented at the 26th Annual Meeting of the European Thyroid Association, Milan, Italy, 1999, and at the 12th International Thyroid Congress, Kyoto, Japan, 2000.

Abbreviations: I-, Iodide; MNG, multinodular goiter; NIS, Na+/I- symporter; Tg, thyroglobulin; Tg-I, T4-containing thyroglobulin; ThOX, thyroid oxidase; TPO, thyroperoxidase; TSHr, TSH receptor.




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