title: Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas.
abstract: 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 H(2)O(2)-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T(4)-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. T(4)-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 H(2)O(2)-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 T(4)-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.
authors.affiliation: Histology, Université Catholique de Louvain Medical School, B-1070 Brussels, Belgium.
authors.forename: A-C
authors.initials: AC
authors.lastname: Gérard
authors.forename: C
authors.initials: C
authors.lastname: Daumerie
authors.forename: C
authors.initials: C
authors.lastname: Mestdagh
authors.forename: S
authors.initials: S
authors.lastname: Gohy
authors.forename: C
authors.initials: C
authors.lastname: De Burbure
authors.forename: S
authors.initials: S
authors.lastname: Costagliola
authors.forename: F
authors.initials: F
authors.lastname: Miot
authors.forename: M-C
authors.initials: MC
authors.lastname: Nollevaux
authors.forename: J-F
authors.initials: JF
authors.lastname: Denef
authors.forename: J
authors.initials: J
authors.lastname: Rahier
authors.forename: B
authors.initials: B
authors.lastname: Franc
authors.forename: J J M
authors.initials: JJ
authors.lastname: De Vijlder
authors.forename: I M
authors.initials: IM
authors.lastname: Colin
authors.forename: M-C
authors.initials: MC
authors.lastname: Many
mesh_terms: D015415:Biomarkers; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D000074623:Dual Oxidases; D005420:Flavoproteins / Q000378:metabolism; D006042:Goiter / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D026901:Membrane Transport Proteins; D019255:NADPH Oxidases; D011989:Receptors, Thyrotropin / Q000378:metabolism; D000076988:Sulfate Transporters; D027981:Symporters / Q000378:metabolism; D013954:Thyroglobulin / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D013974:Thyroxine / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D000074623:Dual Oxidases; D005420:Flavoproteins; D007453:Iodide Peroxidase; D007455:Iodine; D026901:Membrane Transport Proteins; D019255:NADPH Oxidases; D011989:Receptors, Thyrotropin; D000076988:Sulfate Transporters; D027981:Symporters; D013954:Thyroglobulin; D013974:Thyroxine; D000099209:Sodium-Iodide Symporters; C085609:SLC26A4 protein, human; C431513:DUOX1 protein, human; C431515:DUOX2 protein, human