Alterations of NIS expression in functioning thyroid nodules

Yıl 2010, Cilt: 20 Sayı: 6, 285 - 292, 20.12.2010

Hülya Ilıksu Gözü Dilek Yavuzer Handan Kaya Selahattin Vural Haluk Sargın Cem Gezen Mehmet Sargın Sema Akalın

Öz

Objectives: This study aimed to analyze both the level and the cell site of the sodium-iodide symporter NIS protein expression in autonomously functioning thyroid nodules AFTNs and extranodular thyroid tissues. In addition, this study sought to compare the clinical results of patients with the levels of human NIS hNIS protein expression. Patients and Methods: The histological slides consisted of 36 AFTNs and 31 extranodular thyroid tissues from 28 patients 5 males, 23 females; mean age 54.5±11.0 years; range 37 to 72 years who underwent surgery for toxic multinodular goitre. The expression of NIS protein was investigated by immunohistochemistry in paraffinembedded tissue sections using anti-hNIS monoclonal antibody by the labeled streptavidin-biotin method. Results: The percentage of hNIS positive follicular cells was significantly higher in the AFTNs 13.33±12.09 than in the extranodular thyroid tissues 1.35±3.03 . Staining for hNIS was mostly confined to the cell membrane in the AFTNs 88.9% and in the extranodular thyroid tissues 54.5% . The clinical parameters and nodule volume did not establish any correlation with hNIS immunoreactivity. Conclusion: Our data indicate that functioning nodules express higher amounts of NIS protein than the extranodular thyroid tissue, but the level of hNIS immunoreactivity was lower than had been reported in the previous literature. This result may be due to interindividual variability between different populations, and iodine status. Furthermore, the localization of the NIS protein might not give an indication of its functional status.

Anahtar Kelimeler

Genetic transcription, sodium-iodide symporter, thyroid gland/surgery, thyroid neoplasms

Fonksiyone tiroid nodüllerinde NIS ekspresyonundaki değişiklikler

Öz

Amaç: Bu çalışmada, otonom olarak fonksiyone tiroid nodüllerinde FTN ve ekstranodüler tiroid dokusunda sodyum-iyot simporter NIS protein ekspresyonunun seviyesi ve hücredeki yerleşim yeri araştırıldı. Bunun yanı sıra bu çalışmada hastaların klinik bulgularıyla human NIS hNIS protein ekspresyonu seviyeleri karşılaştırıldı.Hastalar ve Yöntemler: Histolojik kesitler, toksik multinodüler guatr nedeniyle ameliyat olmuş 28 hastaya 5 erkek, 23 kadın; ort. yaş 54.5±11.0 yıl; dağılım 37-72 yıl ait 36 otonom FTN ve 31 ekstranodüler tiroid dokusundan oluşmaktaydı. Parafine gömülmüş bu doku kesitlerinde, NIS protein ekspresyonu, labeled streptavidin-biotin yöntemi ile anti-hNIS monoklonal antikoru kullanılarak immünohistokimyasal olarak araştırıldı.Bulgular: Otonom fonksiyone tiroid nodüllerindeki hNIS pozitif hücrelerin oranı 13.33±12.09 ekstranodüler tiroid dokusuna 1.35±3.03 göre anlamlı olarak daha yüksekti. hNIS boyanması genellikle otonom FTN’lerde %88.9 ve ekstranodüler tiroid dokusunda %54.5 hücre zarı ile sınırlı idi. Klinik parametreler ve nodül volümü ile hNIS immünoreaktivitesi ilişkili bulunmadı.Sonuç: Bizim verilerimiz, fonksiyone nodüllerde ekstranodüler tiroid dokusuna göre daha fazla miktarda NIS protein ekspresyonu olduğunu gösterdi, fakat, hNIS immünoreaktivitesi literatürde daha önce bildirilenlere göre daha düşük seviyelerde bulundu. Bu durum değişik toplumlardaki kişisel farklılıklara ve mevcut iyodin durumuna bağlı olabilir. Ayrıca NIS proteininin hücredeki yerleşim yeri NIS’nin fonksiyonunun göstergesi olmayabilir

Anahtar Kelimeler

Genetik transkripsiyon, sodyum-iyot simporter, tiroid bezi/cerrahi, tiroid tümörleri

Kaynakça

• Carrasco N. Iodide transport in the thyroid gland. Biochim Biophys Acta 1993;1154:65-82.
• Dohán O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev 2003;24:48-77.
• Bizhanova A, Kopp P. Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology 2009;150:1084-90.
• Nilsson M. Iodide handling by the thyroid epithelial cell. Exp Clin Endocrinol Diabetes 2001;109:13-7.
• Dohán O, Carrasco N. Advances in Na(+)/I(-) symport- er (NIS) research in the thyroid and beyond. Mol Cell Endocrinol 2003;213:59-70.
• Eskandari S, Loo DD, Dai G, Levy O, Wright EM, Carrasco N. Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. J Biol Chem 1997; 272:27230-8.
• Joba W, Spitzweg C, Schriever K, Heufelder AE. Analysis of human sodium/iodide symporter, thy- roid transcription factor-1, and paired-box-protein-8 gene expression in benign thyroid diseases. Thyroid 1999;9:455-66.
• Dai G, Levy O, Carrasco N. Cloning and charac- terization of the thyroid iodide transporter. Nature 1996;379:458-60.
• Deleu S, Allory Y, Radulescu A, Pirson I, Carrasco N, Corvilain B, et al. Characterization of autonomous thyroid adenoma: metabolism, gene expression, and pathology. Thyroid 2000;10:131-40.
• Caillou B, Troalen F, Baudin E, Talbot M, Filetti S, Schlumberger M, et al. Na+/I- symporter distribution in human thyroid tissues: an immunohistochemical study. J Clin Endocrinol Metab 1998;83:4102-6.
• McDougall IR. In vivo radionuclide tests and imag- ing. In: Braverman LE, Utiger RD, editors. Werner and Ingbar’s The Thyroid. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 309-28.
• Riesco-Eizaguirre G, Santisteban P. A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol 2006;155:495-512.
• Carvalho DP, Ferreira AC. The importance of sodium/ iodide symporter (NIS) for thyroid cancer manage- ment. Arq Bras Endocrinol Metabol 2007;51:672-82.
• Faggiano A, Caillou B, Lacroix L, Talbot M, Filetti S, Bidart JM, et al. Functional characterization of human thyroid tissue with immunohistochemistry. Thyroid 2007;17:203-11.
• Syrenicz A, Wolny M, Kram A, Sworczak K, Syrenicz M, Garanty-Bogacka B, et al. Analysis of the sodium iodide symporter expression in histological slides from a nodular goiter. Arch Med Res 2007;38:219-26.
• Tonacchera M, Viacava P, Agretti P, de Marco G, Perri A, di Cosmo C, et al. Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein. J Clin Endocrinol Metab 2002;87:352-7.
• Tonacchera M, Viacava P, Fanelli G, Agretti P, De Marco G, De Servi M, et al. The sodium-iodide sym- porter protein is always present at a low expression and confined to the cell membrane in nonfunctioning nonadenomatous nodules of toxic nodular goitre. Clin Endocrinol (Oxf) 2004;61:40-5.
• Ueda D. Sonographic measurement of the volume of the thyroid gland in healthy children. Acta Paediatr Jpn 1989;31:352-4.
• Russo D, Bulotta S, Bruno R, Arturi F, Giannasio P, Derwahl M, et al. Sodium/iodide symporter (NIS) and pendrin are expressed differently in hot and cold nodules of thyroid toxic multinodular goiter. Eur J Endocrinol 2001;145:591-7.
• Jhiang SM, Cho JY, Ryu KY, DeYoung BR, Smanik PA, McGaughy VR, et al. An immunohistochemical study of Na+/I- symporter in human thyroid tissues and salivary gland tissues. Endocrinology 1998;139:4416-9.
• Castro MR, Bergert ER, Beito TG, McIver B, Goellner JR, Morris JC. Development of monoclonal antibodies against the human sodium iodide symporter: immu- nohistochemical characterization of this protein in thyroid cells. J Clin Endocrinol Metab 1999;84:2957-62.
• Mishra A, Pal L, Mishra SK. Distribution of Na+/I- symporter in thyroid cancers in an iodine-deficient population: an immunohistochemical study. World J Surg 2007;31:1737-42.
• Scipioni A, Ferretti E, Soda G, Tosi E, Bruno R, Costante G, et al. hNIS protein in thyroid: the iodine supply influences its expression and localization. Thyroid 2007;17:613-8.
• Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, et al. Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tis- sue microarrays and conventional sections. J Clin Endocrinol Metab 2003;88:1880-8.
• Erdoğan G, Erdogan MF, Emral R, Baştemir M, Sav H, Haznedaroğlu D, et al. Iodine status and goiter prevalence in Turkey before mandatory iodization. J Endocrinol Invest 2002;25:224-8.
• Dohán O, Baloch Z, Bánrévi Z, Livolsi V, Carrasco N. Rapid communication: predominant intracellu- lar overexpression of the Na(+)/I(-) symporter (NIS) in a large sampling of thyroid cancer cases. J Clin Endocrinol Metab 2001;86:2697-700.
• Goto A, Uchino S, Noguchi S, Wakiya S, Watanabe Y, Murakami T, et al. NIS mRNA expression level in resected thyroid tissue as a marker of postopera- tive hypothyroidism after subtotal thyroidectomy in patients with Graves’ disease. Endocr J 2008;55:73-81.
• Syrenicz A, Wolny M, Kram A, Sworczak K, Syrenicz M, Garanty-Bogacka B, et al. Correlation between level of sodium/iodide symporter expression in tissue sec- tions and some clinical parameters in patients with nodular goiter. Arch Med Sci 2006;2:240-6.