TY - JOUR
T1 - Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake
AU - Mian, Caterina
AU - Barollo, Susi
AU - Pennelli, Gianmaria
AU - Pavan, Nicodemo
AU - Rugge, Massimo
AU - Pelizzo, Maria Rosa
AU - Mazzarotto, Renzo
AU - Casara, Dario
AU - Nacamulli, Davide
AU - Mantero, Franco
AU - Opocher, Giuseppe
AU - Busnardo, Benedetto
AU - Girelli, Maria Elisa
PY - 2008/1
Y1 - 2008/1
N2 - 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 ( 131I) 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 131I; and Group 3, 13 recurrences incapable of trapping 131I. mRNA levels of thyroid genes (sodium/iodide symporter NIS, thyroglobulin, thyroperoxidase 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 131I 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 131I 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 GLUT-1 gene expression supports the use of positron emission tomography with specific tracers in clinical management of such cancers; and (3) BRAF V600E point mutations may lead to less differentiated phenotypes, suggesting a worse prognosis.
AB - 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 ( 131I) 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 131I; and Group 3, 13 recurrences incapable of trapping 131I. mRNA levels of thyroid genes (sodium/iodide symporter NIS, thyroglobulin, thyroperoxidase 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 131I 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 131I 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 GLUT-1 gene expression supports the use of positron emission tomography with specific tracers in clinical management of such cancers; and (3) BRAF V600E point mutations may lead to less differentiated phenotypes, suggesting a worse prognosis.
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U2 - 10.1111/j.1365-2265.2007.03008.x
DO - 10.1111/j.1365-2265.2007.03008.x
M3 - Article
C2 - 17854396
AN - SCOPUS:36949011598
VL - 68
SP - 108
EP - 116
JO - Clinical Endocrinology
JF - Clinical Endocrinology
SN - 0300-0664
IS - 1
ER -