Endocrine Abstracts

Radioiodide therapy of thyroid cancer represents the most effective form of systemic radiotherapy available to the clinician today. The ability of thyroid cancer cells to concentrate iodide is induced by expression in the follicular cell membrane of the sodium iodide symporter, NIS. Some thyroid cancers lack expression of this protein and therefore the ability to concentrate iodide, making them insensitive to 131-I therapy. Several investigators have characterized the expression of NIS mRNA and protein in thyroid cancers and have reported variable results. We recently reported examination of NIS protein expression, as determined by immunohistochemistry, in tumors of 60 patients with metastatic thyroid cancer and found that positive immunostaining of the primary tumor predicted uptake by the metastatic tumor in 84%, and that negative immunostaining predicted absent RAI uptake in 59% of cases. Thus, NIS immunostaining of the tumors had substantial ability to predict behavior of metastatic disease, but several discrepancies were observed. Thyroid hormone therapy at the time of sampling the tumor impaired the correlation between immunostaining results and iodide uptake. It is now clear that several mechanisms play a role in explaining the discrepancy between NIS expression and uptake including 1) impaired targeting of NIS to the membrane; 2) abnormal glycosylation or other post-translational modification alterations; 3) dedifferentiation of cells within the metastatic deposit. Methods of improving membrane targeting, recovering normal post-translational modifications or of removing transcriptional inhibitors, such as hypermethylation are needed to broaden the utility of this effective form of therapy for our patients. Finally, these methods may also prove useful in the management of patients with non-thyroid cancer with radioiodide after NIS gene transfer.