Assessing the sodium-iodide symporter (NIS) in pediatric differentiated thyroid carcinoma

Background: The sodium-iodide symporter (NIS), encoded by the SLC5A5 gene, is essential for iodide uptake and the effectiveness of radioiodide therapy in differentiated thyroid carcinoma (DTC). Data addressing the relationship between NIS transcription and protein expression in pediatric DTC remain limited. Methods: We conducted a retrospective cohort study of pediatric and adolescent patients with DTC, evaluating NIS protein expression by immunohistochemistry in tumor and adjacent nontumoral thyroid tissues and tumor SLC5A5 mRNA expression by quantitative real-time PCR. Clinical, pathological, molecular, and treatment-related variables were analyzed. Results: We analyzed DTC samples from 92 patients diagnosed under the age of 19. NIS was present at significantly lower levels in tumor cells than in adjacent nontumoral cells (odds ratio (OR): 106.8; 95% (CI): 30.7-337.5; P < 0.0001). NIS was only detected in 20/92 of tumor samples, while SLC5A5 was expressed in 36/70 of tumor samples. No associations were found between NIS expression or SLC5A5 expression and clinical or histological features, metastasis, iodide-131 (I-131) activity, or treatment response. A dissociation between gene expression and protein detection was observed. Despite reduced tumoral NIS protein expression, most patients achieved an excellent response to radioiodide therapy. Conclusion: This study highlights significant differences in NIS expression between pediatric thyroid tumors and adjacent nontumoral tissue, with a lower proportion of NIS-positive tumors compared with SLC5A5-high cases. No associations were observed between NIS protein detection or SLC5A5 expression and clinical features, histology, tumor aggressiveness, or treatment response.