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

Caterina Mian, Susi Barollo, Gianmaria Pennelli, Nicodemo Pavan, Massimo Rugge, Maria Rosa Pelizzo, Renzo Mazzarotto, Dario Casara, Davide Nacamulli, Franco Mantero, Giuseppe Opocher, Benedetto Busnardo, Maria Elisa Girelli

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Abstract

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.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalClinical Endocrinology
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Iodine
Thyroglobulin
Recurrence
Neoplasms
Genes
Gene Expression
Mutation
Hexokinase
Mutation Rate
Thyroid Neoplasms
Point Mutation
Positron-Emission Tomography
Papillary Thyroid cancer
Thyroid Gland
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • Endocrinology

Cite this

Mian, C., Barollo, S., Pennelli, G., Pavan, N., Rugge, M., Pelizzo, M. R., ... Girelli, M. E. (2008). Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. Clinical Endocrinology, 68(1), 108-116. https://doi.org/10.1111/j.1365-2265.2007.03008.x

Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. / Mian, Caterina; Barollo, Susi; Pennelli, Gianmaria; Pavan, Nicodemo; Rugge, Massimo; Pelizzo, Maria Rosa; Mazzarotto, Renzo; Casara, Dario; Nacamulli, Davide; Mantero, Franco; Opocher, Giuseppe; Busnardo, Benedetto; Girelli, Maria Elisa.

In: Clinical Endocrinology, Vol. 68, No. 1, 01.2008, p. 108-116.

Research output: Contribution to journalArticle

Mian, C, Barollo, S, Pennelli, G, Pavan, N, Rugge, M, Pelizzo, MR, Mazzarotto, R, Casara, D, Nacamulli, D, Mantero, F, Opocher, G, Busnardo, B & Girelli, ME 2008, 'Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake', Clinical Endocrinology, vol. 68, no. 1, pp. 108-116. https://doi.org/10.1111/j.1365-2265.2007.03008.x
Mian, Caterina ; Barollo, Susi ; Pennelli, Gianmaria ; Pavan, Nicodemo ; Rugge, Massimo ; Pelizzo, Maria Rosa ; Mazzarotto, Renzo ; Casara, Dario ; Nacamulli, Davide ; Mantero, Franco ; Opocher, Giuseppe ; Busnardo, Benedetto ; Girelli, Maria Elisa. / Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. In: Clinical Endocrinology. 2008 ; Vol. 68, No. 1. pp. 108-116.
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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

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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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