Differentiated Thyroid Carcinoma That Express Sodium-Iodide Symporter Have a Lower Risk of Recurrence for Children and Adolescents

Abstract

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). ABSTRACT737

Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma?

“…The former study assessed the expression of NIS in the malignant tumor and compared to benign lesions as a substitute of normal thyroid. The authors did not find a significant difference between benign and malignant thyroid lesions (Patel et al 2002). Because the overall recurrence risk was increased for those tumors that had undetectable NIS expression, the authors suggested that NIS expression is a favorable prognostic indicator for DTC in children and adolescents (Patel et al 2002).…”

“…The authors did not find a significant difference between benign and malignant thyroid lesions (Patel et al 2002). Because the overall recurrence risk was increased for those tumors that had undetectable NIS expression, the authors suggested that NIS expression is a favorable prognostic indicator for DTC in children and adolescents (Patel et al 2002). Additionally, the authors studied patients up to 21 years of age and only two cases under the age of 10.…”

“…Accordingly, it has been suggested that the expression of NIS, as well as other proteins involved in iodine uptake and metabolism in pediatric patients, is higher than their expression in adults (Patel et al 2002, Faggiano et al 2004, Espadinha et al 2009). Nonetheless, in some series, there is a higher prevalence of extrathyroidal extension, regional lymph node involvement and distant metastases in younger children than in adolescents (Alessandri et al 2000, Jarzab et al 2005, Dinauer et al 2008, Lazar et al 2009, O'Gorman et al 2010, Rivkees et al 2011, Francis et al 2015.…”

“…Either younger children were commonly underrepresented and/or patients over the age of 18 years at diagnosis were also included into the pediatric group. Moreover, only two studies specifically addressed the expression of iodinemetabolizing genes in pediatric patients (Patel et al 2002, Espadinha et al 2009). The former study assessed the expression of NIS in the malignant tumor and compared to benign lesions as a substitute of normal thyroid.…”

Comments to part of the American thyroid association guidelines for the management of thyroid nodules in children

“…Указанные молекулярные различия могут являться одним из благоприятных условий лучшего ответа на РЙТ у детей, чем у взрослых с ПРЩЖ, что, вероятно, объ-ясняет более низкую смертность и более редкое про-грессирование до низкодифференцированных типов опухолей у детей. В подтверждение этой гипотезы приводится небольшое исследование у детей (n = 23), в котором было выявлено, что наличие отдаленных метастазов и рецидивов рака было ассоциировано только с опухолями с неопределяемым при иммуно-гистохимическом анализе НЙС, а для достижения ремиссии в этих случаях потребовались значительно большие дозы радиоактивного йода [12].…”