Molecular characteristics in papillary thyroid cancers (PTCs) with no I-131 uptake

Objective Papillary thyroid cancers (PTCs) with no iodine uptake have an aggressive behaviour and a poor prognosis. The aim of our study was to characterize, at molecular level, a subset of PTC with no 131 iodine (1311) uptake. Design and methods Forty-eight cancer tissues were divided into three groups: Group 1, 28 primary cancers; Group 2, 7 recurrences capable of trapping 13 11; and Group 3, 13 recurrences incapable of trapping I-131. mRNA levels of thyroid genes (sodium/iodide symporter NIS, thyroglobulin, thyroperoxiclase and pendrin) and glycolytic metabolism genes (GLUT-1, hexokinase I and II) and BRAF mutations were evaluated in the different groups. Results Cancers with no I-131 uptake had slightly reduced NIS, significantly reduced thyroglobulin (P<0.01), thyroperoxidase (P=0.01) and pendrin (P=0.03) and significantly increased GLUT-1 (P = 0.01) gene expression levels; and a high frequency of BRAF mutations (77%). BRAF(V600E) mutation, in both primary and metastatic thyroid cancers, is associated with a marked drop in thyroperoxidase (29-fold) and pendrin (20-fold) expression and a considerable increase (five-fold) in GLUT-1 expression. Conclusions (1) The loss of I-131 uptake in recurrences depends not only on a decrease in NIS gene, but possibly on a reduction in the molecules regulating its intracellular metabolism; (2) the high GLUTA gene expression supports the use of positron emission tomography with specific tracers in clinical management of such cancers; and (3) BRAT(V600E) point mutations may lead to less differentiated phenotypes, suggesting a worse prognosis.