{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:48:23Z","timestamp":1778618903751,"version":"3.51.4"},"reference-count":42,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the<jats:italic>SLC5A5<\/jats:italic>gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied<jats:italic>SLC5A5<\/jats:italic>expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series,<jats:italic>SLC5A5<\/jats:italic>expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring<jats:italic>BRAF<\/jats:italic>V600E mutation. Analysis of<jats:italic>SLC5A5<\/jats:italic>expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and\/or distant metastases or harboring<jats:italic>RAS<\/jats:italic>,<jats:italic>BRAF<\/jats:italic>and\/or<jats:italic>TERT<\/jats:italic>promoter (<jats:italic>TERT<\/jats:italic>p) mutations presented significantly less<jats:italic>SLC5A5<\/jats:italic>expression. Regarding immunohistochemistry, 12\/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for<jats:italic>BRAF<\/jats:italic>,<jats:italic>NRAS<\/jats:italic>and<jats:italic>TERT<\/jats:italic>p mutations.<jats:italic>SLC5A5<\/jats:italic>mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving<jats:italic>BRAF<\/jats:italic>,<jats:italic>RAS<\/jats:italic>and<jats:italic>TERT<\/jats:italic>p. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane.<jats:italic>SLC5A5<\/jats:italic>mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.<\/jats:p>","DOI":"10.1530\/ec-17-0302","type":"journal-article","created":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T01:11:13Z","timestamp":1515028273000},"page":"78-90","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":58,"title":["NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features"],"prefix":"10.1530","volume":"7","author":[{"given":"Catarina","family":"Tavares","sequence":"first","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Coelho","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"4Institute of Biomedical Sciences of Abel Salazar (ICBAS), Porto, Portugal"}]},{"given":"Catarina","family":"Eloy","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"}]},{"given":"Miguel","family":"Melo","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"5Department of Endocrinology, Diabetes and Metabolism, University and Hospital Center of Coimbra, Coimbra, Portugal"},{"name":"6Medical Faculty, University of Coimbra, Coimbra, Portugal"}]},{"given":"Adriana Gaspar","family":"da Rocha","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"7Public Health Unit, ACeS Baixo Mondego, Coimbra, Portugal"}]},{"given":"Ana","family":"Pestana","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"}]},{"given":"Rui","family":"Batista","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"}]},{"given":"Luciana Bueno","family":"Ferreira","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"}]},{"given":"Elisabete","family":"Rios","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"},{"name":"8Department of Pathology, Medical Faculty of the University of Porto, Porto, Portugal"},{"name":"9Department of Pathology, Hospital de S. Jo\u00e3o, Porto, Portugal"}]},{"given":"Samia","family":"Selmi-Ruby","sequence":"additional","affiliation":[{"name":"10Inserm UMR-S1052, CNRS UMR5286, Centre de Recherche en Canc\u00e9rologie de Lyon, Lyon, France"}]},{"given":"Bruno","family":"Cavadas","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"4Institute of Biomedical Sciences of Abel Salazar (ICBAS), Porto, Portugal"}]},{"given":"Lu\u00edsa","family":"Pereira","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"}]},{"given":"Manuel","family":"Sobrinho Sim\u00f5es","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"},{"name":"8Department of Pathology, Medical Faculty of the University of Porto, Porto, Portugal"},{"name":"9Department of Pathology, Hospital de S. Jo\u00e3o, Porto, Portugal"}]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"1Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Porto, Portugal"},{"name":"2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"3Medical Faculty of the University of Porto, Porto, Portugal"},{"name":"8Department of Pathology, Medical Faculty of the University of Porto, Porto, Portugal"}]}],"member":"416","reference":[{"key":"ref221","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1007\/s10147-013-0620-z","article-title":"Low expression of sodium iodide symporter expression in aggressive variants of papillary thyroid carcinoma","volume":"19","year":"2014","journal-title":"International Journal of Clinical Oncology"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1677\/erc.1.01119","article-title":"The oncogene BRAF V600E is associated with a high 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tumors with synchronous cervical metastasis","volume":"119","year":"2009","journal-title":"Laryngoscope"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"4416","DOI":"10.1210\/endo.139.10.6329","article-title":"An immunohistochemical study of Na+\/I- symporter in human thyroid tissues and salivary gland tissues","volume":"139","year":"1998","journal-title":"Endocrinology"},{"key":"ref131","first-page":"2697","article-title":"Rapid communication: predominant intracellular overexpression of the Na(+)\/I(-) symporter (NIS) in a large sampling of thyroid cancer cases","volume":"86","year":"2001","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref321","doi-asserted-by":"publisher","first-page":"201499","DOI":"10.1210\/jc.2013-3734","article-title":"promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas of and https org","author":"MeloMda","journal-title":"Journal Clinical Endocrinology 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Pathology and Genetics of Tumours of Endocrine Organs","year":"2004"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1677\/ERC-07-0130","article-title":"BRAFV600E mutation, but not RET\/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer","volume":"15","year":"2008","journal-title":"Endocrine-Related Cancer"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/BF03347392","article-title":"Relationship of sodium\/iodide symporter expression with I131 whole body scan uptake between primary and metastatic lymph node papillary thyroid carcinomas","volume":"30","year":"2007","journal-title":"Journal of Endocrinological Investigation"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0002-9440(10)63272-5","article-title":"Evidence for transcriptional and posttranscriptional alterations of the sodium\/iodide symporter expression in hypofunctioning benign and malignant thyroid tumors","volume":"165","year":"2004","journal-title":"American Journal of Pathology"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1586\/era.12.96","article-title":"Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma","volume":"12","year":"2012","journal-title":"Expert Review of Anticancer Therapy"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1530\/EJE-08-0505","article-title":"Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers","volume":"160","year":"2009","journal-title":"European Journal of Endocrinology"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"5627","DOI":"10.1210\/jcem.86.11.8048","article-title":"Immunohistochemical analysis of sodium iodide symporter expression in metastatic 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