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Association of Low Sodium-Iodide Symporter Messenger Ribonucleic Acid Expression in Malignant Thyroid Nodules with Increased Intracellular Protein Staining

Thyroid Study Unit (LIM-25) (A.K.M.B.S., I.G.S.R., A.L.R.G., M.K., E.K.T., G.M.-N., R.Y.A.C.), Division of Endocrinology, Division of Pathology (V.A.F.A.), and Nuclear Medicine Center (C.A.B., T.W.), Department of Radiology, University of São Paulo Medical School, 05403-900 São Paulo, Brazil; Adolfo Lutz Institute (C.T.K.), São Paulo Public Health Service, 01246-903 São Paulo, Brazil; and Department of Head and Neck Surgery (C.U.M.F., M.A.V.K.), University of Santo Amaro, 04743-003 São Paulo, Brazil

Address all correspondence and requests for reprints to: Rosalinda Y. A. Camargo, Hospital das Clínicas, FMUSP, Av. Enéas Carvalho de Aguiar, 255, 2 A Bl 7, CEP 05403-900, São Paulo, Brazil. E-mail: ryasato{at}uol.com.br.

Context: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules.

Objective: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls).

Design: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples.

Results: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%).

Conclusion: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.