Endocrine Abstracts

The prognosis of differentiated thyroid cancers is influenced by their ability to accumulate iodine and hence their sensitivity to ablative ¹³¹I therapy. Radioiodine concentration is mediated by the sodium-iodide symporter (NIS). We have previously identified PTTG and fibroblast growth factor-2 (FGF-2) as potential prognostic indicators for differentiated thyroid cancers. Furthermore, we demonstrated that FGF-2 reduces iodide uptake in FRTL5 cells and primary human thyrocytes. We postulated that NIS expression may be related to the outcome of thyroid cancers and that NIS expression and iodide uptake in thyroid cells may be influenced by PTTG. We compared expression of NIS in 20 differentiated thyroid cancers with 11 normal thyroids. Gene expression was related to tumour stage at presentation and to recurrence early during follow-up. Subsequently, we assessed the effects on NIS expression and iodide uptake in FRTL5 thyroid cells and primary human thyroid cultures following transient transfection of PTTG. NIS mRNA and protein expression were significantly reduced in carcinomas when compared with normal samples (40% reduction, P=0.02). NIS mRNA was significantly lower in recurrent compared with non recurrent cancers (n=5, P=0.013) and in those with metastasis at presentation compared with non-metastatic tumours (n=3, P=0.01). Taking into account known prognostic indicators of age, gender, size and type of tumour, we found an independent association between increased NIS expression and distant metastasis at presentation (R²=0.83, P<0.001). Transient transfection of wild type PTTG significantly reduced ¹²⁵I uptake in FRTL5 cells (45% reduction compared with vector only (VO), P=0.004) and in primary human thyrocytes (39% reduction compared with VO, P=0.03). Moreover, transient transfection of PTTG in primary cultures lead to a significant reduction in NIS mRNA expression (90% reduction, P=0.008) and a significant increase in FGF-2 expression (3.2-fold induction, P=0.01) when compared to control, suggesting that PTTG-mediated effects may be through upregulation of FGF-2. We conclude that NIS expression is a potential indicator of prognosis for differentiated thyroid cancer and that PTTG overexpression leads to reduced NIS expression and iodide uptake in thyroid cells in vitro.