The significantly lower SLC5A5 expression in cases presenting vascular invasion and extrathyroidal extension suggests that a decreased SLC5A5 expression may be associated to an aggressive tumor behavior and thus may help to characterize patients at risk for poor therapy response. Further analysis of TCGA data demonstrated that SLC5A5 expression is significantly lower in cases that had locoregional recurrences and/or distant metastases (Fig. 2E). Given the high prognostic impact of recurrences and distant metastases (38), these results suggest that a lower expression of SLC5A5 in thyroid primary tumor seems to be associated with features of higher aggressiveness of the primary tumor and also with a worse prognosis and with poor response to therapy. Two groups reported that SLC5A5 was significantly less expressed in DTCs larger than 2 cm and PTCs larger than 1 cm (in comparison to ≤2 cm and <1 cm, respectively) (1, 39), TCGA results corroborated the literature by showing that larger PTCs (>2 cm) expressed significantly less SLC5A5 compared to those with ≤2 cm. Since larger tumors are associated with higher recurrence rates and worse prognosis (40, 41), the significantly lower SLC5A5 expression in tumors larger than 2 cm may be considered as an additional fact linking lower SLC5A5 mRNA expression with higher tumor aggressiveness. Nevertheless, we must interpret this information carefully: larger tumors may present higher levels of necrosis/fibrosis and also additional non-carcinomatous tissue as part of the nodule, which may contribute to a lower SLC5A5 expression. In our series, we did not include microcarcinomas, so the group of tumors with ≤2 cm was very small, precluding any meaningful analysis (data not shown).