Tonacchera Massimo, Viacava Paolo, Fanelli Giovanni, Agretti Patrizia, De Marco Giuseppina, De Servi Melissa, Di Cosmo Catia, Chiovato Luca, Pinchera Aldo, Vitti Paolo
Dipartimento di Endocrinologia e Metabolismo, Centro Eccellenza Ambisen, Universita di Pisa, Pisa, Italy.
Clin Endocrinol (Oxf). 2004 Jul;61(1):40-5. doi: 10.1111/j.1365-2265.2004.02047.x.
The sodium-iodide (Na(+)/I(-)) symporter (NIS) is known to be overexpressed in toxic adenomas and in about half of benign solitary nonfunctioning adenomas of the thyroid. In nonfunctioning adenomas, however, the protein is localized mainly in the cytoplasm and fails to reach the basolateral membrane of the follicular cell where it is found in normal thyroid tissue and in hyperfunctioning adenomas. Our aim was to study both the level of expression and the cell localization of NIS in nonfunctioning nonadenomatous nodules of toxic nodular goitre.
Tissue specimens from nine patients who were submitted to surgery for toxic or functionally autonomous goitre were studied. Tissues from 12 patients who underwent lobectomy for a toxic thyroid adenoma were used as controls.
Tissue sections embedded in paraffin were stained with haematoxylin-eosin for histological evaluation and for immunohistochemistry using a monoclonal antibody that recognized human (h) NIS.
Functioning and nonfunctioning nodules scattered in multinodular goitres consisted of unencapsulated micro/macrofollicular aggregates. All toxic adenomas were characterized by a micro/macrofollicular pattern of growth and histological examination showed that they were surrounded by a capsule. Like the 12 toxic adenomas, all the 14 functioning hyperplastic nodules and two adenomas of toxic multinodular goitre showed a high level of hNIS protein expression with respect to the normal collateral parenchyma and, in all cases, the protein was confined to the cell membrane.
Contrary to what was observed for solitary nonfunctioning thyroid adenomas, all the 19 nonfunctioning hyperplastic nodules showed a very low hNIS and this was always confined to the cell membrane. These data suggest that the mechanisms leading to loss of iodide uptake in nonfunctioning hyperplastic nodules of toxic multinodular goitre are different from those that act on solitary nonfunctioning follicular adenomas.
已知钠-碘(Na⁺/I⁻)同向转运体(NIS)在毒性腺瘤以及约半数甲状腺良性孤立性无功能腺瘤中过表达。然而,在无功能腺瘤中,该蛋白主要定位于细胞质,无法到达滤泡细胞的基底外侧膜,而在正常甲状腺组织和功能亢进性腺瘤中该蛋白则位于此处。我们的目的是研究毒性结节性甲状腺肿无功能非腺瘤性结节中NIS的表达水平和细胞定位。
对9例因毒性或功能自主性甲状腺肿接受手术的患者的组织标本进行研究。将12例因毒性甲状腺腺瘤接受叶切除术患者的组织用作对照。
将石蜡包埋的组织切片用苏木精-伊红染色进行组织学评估,并使用识别人类(h)NIS的单克隆抗体进行免疫组织化学检测。
多结节性甲状腺肿中散在的功能性和无功能性结节由未被包裹的微/大滤泡聚集体组成。所有毒性腺瘤均具有微/大滤泡生长模式,组织学检查显示它们被包膜包围。与12例毒性腺瘤一样,所有14个功能性增生性结节和2个毒性多结节性甲状腺肿腺瘤相对于正常旁侧实质均显示高水平的hNIS蛋白表达,并且在所有情况下,该蛋白均局限于细胞膜。
与孤立性无功能甲状腺腺瘤的情况相反,所有19个无功能增生性结节均显示极低的hNIS,并且总是局限于细胞膜。这些数据表明,导致毒性多结节性甲状腺肿无功能增生性结节碘摄取丧失的机制不同于作用于孤立性无功能滤泡性腺瘤的机制。