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


METHODS
Forty-eight cancer tissues were divided into three groups: Group 1, 28 primary cancers; Group 2, 7 recurrences capable of trapping (131)I; and Group 3, 13 recurrences incapable of trapping (131)I. 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 (131)I 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 (131)I 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.
Mian
Caterina
C
Endocrinology Unit, Department of Medical and Surgical Sciences, University of Padua, Italy. caterina.mian@unipd.it
Barollo
Susi
S
Pennelli
Gianmaria
G
Pavan
Nicodemo
N
Rugge
Massimo
M
Pelizzo
Maria Rosa
MR
Mazzarotto
Renzo
R
Casara
Dario
D
Nacamulli
Davide
D
Mantero
Franco
F
Opocher
Giuseppe
G
Busnardo
Benedetto
B
Girelli
Maria Elisa
ME
D000328:Adult; D002277:Carcinoma; D002291:Carcinoma, Papillary; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006593:Hexokinase / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D027981:Symporters / Q000235:genetics; D013954:Thyroglobulin / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult; D000099209:Sodium-Iodide Symporters
D051272:Glucose Transporter Type 1; D006593:Hexokinase; D007457:Iodine Radioisotopes; D026901:Membrane Transport Proteins; D048493:Proto-Oncogene Proteins B-raf; D000076988:Sulfate Transporters; D027981:Symporters; D013954:Thyroglobulin; D000099209:Sodium-Iodide Symporters; C085609:SLC26A4 protein, human; C472074:HK1 protein, human; C482119:BRAF protein, human