Biological differential diagnosis of follicular thyroid tumor and Hürthle cell tumor on the basis of telomere length and hTERT expression

Ann Surg Oncol. 2014 Jul;21(7):2318-25. doi: 10.1245/s10434-014-3552-6. Epub 2014 Feb 22.


Background: The most difficult thyroid tumors to diagnose by histology are follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). Telomere alteration and human telomerase reverse transcriptase (hTERT) expression have been observed in most human cancers and are known to be a feature of malignancy. The purpose of this study was to clarify whether hTERT protein expression and telomere alteration could be applicable biological markers for distinguishing FTC from HCC.

Methods: We investigated a total of 78 thyroid tumor cases, including 14 FTCs, 47 follicular adenomas (FTAs), 5 HCCs, and 12 Hürthle cell adenomas (HCAs). hTERT protein expression was examined by immunohistochemistry, and telomere length was determined by tissue quantitative fluorescence in situ hybridization.

Results: Positivity for hTERT protein expression was observed in 86 % of FTCs and 49 % of FTAs. Telomeres in FTCs were significantly shorter than those in FTAs. All HCCs and HCAs (100 %) expressed hTERT protein. Telomeres in HCCs were significantly shorter than those in HCAs.

Conclusions: Our results suggest that hTERT protein expression and telomere shortening would be applicable as biological markers to distinguish FTC from FTA. Previous studies have suggested that follicular tumor and Hürthle cell tumor should be classified biologically as distinct tumors. All Hürthle cell tumors expressed hTERT protein and HCCs had markedly shortened telomeres, suggesting that follicular tumor and Hürthle cell tumor might be biologically distinct entities.

MeSH terms

  • Adenocarcinoma, Follicular / diagnosis*
  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / metabolism
  • Adenoma / diagnosis*
  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma, Oxyphilic / diagnosis*
  • Adenoma, Oxyphilic / genetics
  • Adenoma, Oxyphilic / metabolism
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Telomerase / metabolism*
  • Telomere Homeostasis / genetics*
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism


  • TERT protein, human
  • Telomerase