Decreased expression of thyrotropin receptor gene suggests a high-risk subgroup for oncocytic adenoma

Eur J Endocrinol. 2004 Mar;150(3):269-76. doi: 10.1530/eje.0.1500269.

Abstract

Objective: The malignancy of thyroid oncocytic tumours, or oncocytomas, is higher than that of follicular tumours. The aim of this study was to investigate the role of thyroid-specific genes in oncocytic tumours and papillary carcinomas.

Design and methods: We compared 29 oncocytic tumours with 12 papillary carcinomas. Real-time quantitative PCR was used to measure the expression of thyroid-specific differentiation markers (thyrotrophin-stimulation hormone receptor (TSHR), thyroglobulin (TG) and Na(+)/I(-) symporter (NIS)), transcription factors (thyroid transcription factor-1 (TTF-1) and paired box gene-8 (PAX8)) and nuclear receptors (peroxisome proliferator-activated receptor (PPARgamma1) and thyroid hormone receptor (TRbeta1)) involved in thyroid carcinogenesis.

Results: TSHR, TTF-1 and TRbeta1 levels were significantly lower in oncocytic tumours than in papillary carcinomas, as a result of specific biological changes in oncocytic tumours. However, PAX8 and PPARgamma1 did not seem to be involved in the process. Applying the criterion of the underexpression of the thyroid-specific differentiation markers, TSHR, TG and NIS, we classified the oncocytic tumours and papillary carcinomas into three groups. In the first, all three markers were underexpressed; in the second, TSHR was normal while TG and NIS were underexpressed; and in the third, only NIS was underexpressed. The expression patterns revealed that 13 of the 24 oncocytic adenomas underexpressing TSHR in our study, as did four of the five oncocytic carcinomas.

Conclusion: Cases of oncocytic adenoma associated with low levels of TSHR could be putative oncocytic carcinomas and should therefore receive adequate follow-up [corrected].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / metabolism
  • Adenocarcinoma, Follicular / pathology
  • Adenocarcinoma, Papillary / genetics
  • Adenocarcinoma, Papillary / metabolism
  • Adenocarcinoma, Papillary / pathology
  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Polymerase Chain Reaction
  • RNA, Neoplasm / chemistry
  • RNA, Neoplasm / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Thyrotropin / biosynthesis*
  • Receptors, Thyrotropin / genetics*
  • Symporters / genetics
  • Symporters / metabolism
  • Thyroglobulin / metabolism
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Thyroid Nuclear Factor 1
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • NKX2-1 protein, human
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • RNA, Neoplasm
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Thyrotropin
  • Symporters
  • Thyroid Nuclear Factor 1
  • Trans-Activators
  • Transcription Factors
  • sodium-iodide symporter
  • Thyroglobulin