The sodium-iodide symporter (NIS) is expressed by papillary (PTC) and follicular (FTC) thyroid carcinoma, and is essential for iodine uptake. We hypothesized that PTC and FTC with detectable NIS immunostaining would be more amenable to radioactive iodine ( 131 I) treatment and follow a more benevolent course. To test this, we determined NIS expression by immunohistochemistry in 23 PTC, 9 FTC, and 12 benign thyroid lesions from children and adolescents. NIS expression was determined by two blinded examiners and graded as absent ϭ 0, minimal ϭ 1, moderate ϭ 2, intense ϭ 3, and very intense ϭ 4. NIS was detected in 35% (eight of 23) of PTC, 44% (four of 9) of FTC, 25% (two of eight) of benign tumors, and 100% (four of four) of autoimmune lesions. The intensity of NIS expression was similar in PTC (0.61 Ϯ 0.24), FTC (0.56 Ϯ 0.24), and benign tumors (0.50 Ϯ 0.33) but was more intense in autoimmune lesions (3.0 Ϯ 0.7, p Ͻ 0.005). Distant metastases were found only among PTC with undetectable NIS (two of 15, 13%), and recurrence developed exclusively from PTC and FTC with undetectable NIS (four of 20, 20% versus zero of 12, p ϭ 0.043). The dose of iodine 131 required to achieve remission in the five patients with PTC who had undetectable NIS (213.3 Ϯ 53 mCi) was greater than that required by patients with similar age and extent of disease for whom NIS expression is unknown (109 Ϯ 22 mCi, p ϭ 0.06). We conclude that NIS expression is associated with a lower risk of recurrence for PTC and FTC of children and adolescents. The NIS is a membrane-bound glycoprotein cotransporter expressed by thyroid, salivary, gastric, mammary, and extraocular tissues (1-4). NIS is essential for the uptake of iodide and thyroid hormone synthesis and is directly related to the level of thyroid differentiation (5-9). NIS expression is controlled by TSH and dependent on TTF-1 as well as [10][11][12][13][14][15]. Because of the central role of NIS in determining radioactive iodine uptake, it has been postulated that thyroid carcinoma that fail to express NIS would be resistant to radioactive iodine ablation (16).In the normal thyroid, NIS expression is unequally distributed around individual thyroid follicles, and is most intense at the basolateral cell border (3,14,(17)(18)(19). Such unequal NIS expression is also found at the macroscopic level, at which radioactive iodine scans reveal patchy uptake in thyroid tumors as well as in autoimmune thyroid disease (20). NIS is most highly expressed by Graves' tissue, in which a diffuse pattern of expression is characteristic (4, 21).
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