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

Clin Endocrinol (Oxf). 2008 Jan;68(1):108-16. doi: 10.1111/j.1365-2265.2007.03008.x. Epub 2007 Sep 14.


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.

Design and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma
  • Carcinoma, Papillary
  • Female
  • Glucose Transporter Type 1 / genetics
  • Hexokinase / genetics
  • Humans
  • In Vitro Techniques
  • Iodine Radioisotopes / metabolism*
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfate Transporters
  • Symporters / genetics
  • Thyroglobulin / genetics
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism*
  • Young Adult


  • Glucose Transporter Type 1
  • Iodine Radioisotopes
  • Membrane Transport Proteins
  • SLC26A4 protein, human
  • Sulfate Transporters
  • Symporters
  • sodium-iodide symporter
  • Thyroglobulin
  • HK1 protein, human
  • Hexokinase
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf