Subcellular distribution of the sodium iodide symporter in benign and malignant thyroid tissues

Membranous expression of the sodium iodide symporter (NIS) is a prerequisite for iodide uptake in thyrocytes. Previous studies reported heterogeneous results on the relative frequency of staining in various pathological conditions of the thyroid. The present study aimed at determining membranous staining by using confocal laser microscopy in benign and malignant thyroid diseases, complemented in a subgroup of patients with recurrent or metastatic disease with functional findings of radioiodine uptake (RIU).

There were 380 malignant thyroid tumors (145 papillary, 51 follicular, 87 Hurthle cell, and 97 undifferentiated thyroid carcinomas [UTC]), 115 benign adenomas, 62 diffuse goiters, 89 inflammatory conditions (Graves', Hashimoto, Thyroiditis deQuervain, and lymphocytic thyroiditis), and 179 normal tissues (NT, fetal, and adult). These were subjected to NIS (two different antibodies) and thyroglobulin (TG) staining and evaluated by confocal microscopy.

In a subgroup of 50 samples from patients with recurrent or metastatic disease, NIS staining was correlated with the RIU. As compared with NT, Graves' patients had significantly higher positive NIS membrane staining (>97% vs. 69%) whereas patients with Hashimoto, lymphocytic thyroiditis but also benign adenomas scored lower than NT (56.7% and 55.8% vs. 69%). Depending on their differentiation NIS staining was significantly lower in thyroid carcinomas in parallel with TG staining with only 1/97 UTCs being positive. RIU was more frequently detectable than NIS staining.

Confocal staining strictly evaluating only membranous expression of NIS has not used on a large scale before this study. We confirm the loss of membranous NIS in benign but more prominently in malignant thyroid tumors. NIS staining of diagnostic tissues cannot be used to predict RIU.