Thyroid-stimulating hormone receptor (TSHR) mediated upregulation of the sodium-iodide symporter (NIS) is routine preparation for ablative radioiodine for thyroid cancer. We quantified expression of NIS protein in thyroid cancers and adjacent normal thyroid tissue in patients with normal TSH at surgery, and patients with TSHR stimulation at surgery.
Formalin-fixed, paraffin embedded specimens were identified in cases with (A) normal TSH (n=25) & (B) TSHR-stimulation (Graves’ disease[n=5] or endogenous TSH >20mIU/L [n=1]). The Ventana Discovery automated immunohistochemistry stainer (Roche, Arizona) was used to stain tumours, adjacent benign thyroid, and external positive/negative controls with a previously validated1 mouse-monoclonal antibody against NIS (MA5-12308, ThermoFisher Scientific, IL). Slides were digitised with the Aperio AT2 Digital Pathology Scanner (Leica Biosystems, Victoria). Intensity of DAB staining was quantified digitally using H-scores and percentage-staining (QuPath, Queens University, Belfast2), then validated manually, using images centred on a high-powered field (20x) with positive staining. Mann-Whitney and Chi-square tests (Fisher's exact) were performed using Stata v14 (Statacorp, Texas).
Median benign thyrocyte NIS expression rate was 9% (IQR 5-28%) in the normal-TSH group, and 45% (IQR 20-74%) in the TSHR-stimulated group (p=0.02); with median H-scores 12 (IQR 5-46) and 62 (IQR 28-159) respectively (p=0.02).
1/25 thyroid cancers in the normal-TSH group was positive for NIS (weak cytoplasmic staining, H-score 1.4). In the TSHR-stimulated group 3/6 thyroid cancers were positive (p=0.02): 2 cases showed strong membranous staining (H-scores 2.4, 218) and 1 case showed weak cytoplasmic/nuclear staining (H-score 7.4).
This study demonstrates that thyroid cancers have negligible expression of NIS in an unstimulated state, and that TSHR stimulation correlates with increased NIS expression in benign and malignant thyroid tissue. As appropriate TSHR stimulation is essential for effective ablation, studies directly comparing preparation with rhTSH vs TSH withdrawal would guide clinical practice and may improve ablation.