RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

Histopathology. 2012 Nov;61(5):833-43. doi: 10.1111/j.1365-2559.2012.04276.x. Epub 2012 Jul 17.

Abstract

Aims: The molecular alterations underlying follicular Hürthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hürthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations.

Methods and results: We investigated a series of 20 follicular Hürthle cell tumours [17 FHCCs and three follicular Hürthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC-positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement.

Conclusions: Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoma, Oxyphilic / genetics*
  • Adenoma, Oxyphilic / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Rearrangement
  • Genes, ras
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Mutation
  • Oncogene Proteins, Fusion / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • Oncogene Proteins, Fusion
  • PAX8-PPARgamma fusion protein, human
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • ret-PTC fusion oncoproteins, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)

Supplementary concepts

  • Thyroid cancer, Hurthle cell