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Detection of RET rearrangements in papillary thyroid carcinoma using RT-PCR and FISH techniques - A molecular and

Thomas Johannes Musholt1, Julia Isabelle Staubitz1, Rafael Jaime Antonio Cámara2

  • 1Section of Endocrine Surgery, Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, D-55131, Mainz, Germany.

European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
|November 26, 2018
PubMed
Abstract

Insights

Fluorescent in situ hybridization (FISH) detects RET rearrangements in papillary thyroid carcinoma (PTC) more effectively than RT-PCR. RET rearrangements correlate with iodine-refractory disease and increased lymph node metastasis risk in PTC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Papillary thyroid carcinoma (PTC) is frequently driven by oncogenic mutations in BRAF, RAS, or RET fusion oncogenes.
  • A subset of PTCs lack these known mutations, presenting a heterogeneous group that complicates prognostic analysis based on underlying genetics.

Purpose of the Study:

  • To compare the diagnostic utility of hybrid-specific reverse transcription polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH) for detecting RET rearrangements in BRAF wild-type PTC.
  • To investigate the clinical significance of RET rearrangements in PTC, specifically their association with iodine avidity and lymph node metastasis.

Main Methods:

  • BRAF wild-type PTC tissues from 56 patients were analyzed.
  • Hybrid-specific RT-PCR was used to detect the predominant RET/PTC1 rearrangement.
  • FISH was employed to identify RET rearrangements, and clinical features were compared between RET-rearranged and non-rearranged cases.

Main Results:

  • RT-PCR identified RET/PTC1 rearrangements in 9% of tumors, while FISH detected RET rearrangements in 16% of cases, including previously unidentified ones.
  • Loss of iodine avidity was significantly associated with RET rearrangements (7/9 tumors), occurring only in rearranged cases (p=0.029).
  • RET rearrangements increased the risk of lymph node metastases eightfold (p=0.010).

Conclusions:

  • FISH is superior to RT-PCR in detecting diverse RET fusion genes in PTC.
  • The presence of RET rearrangements is a significant predictor of iodine-refractory disease and lymph node metastasis in PTC.
  • FISH analysis provides crucial clinical insights for surgical decision-making, particularly regarding lymph node dissection, that RT-PCR alone might miss.
Keywords:
BRAF mutationFluorescent in situ hybridizationIodine avidityLymph node metastasesPapillary thyroid carcinomaPrognostic factorRET/PTC rearrangementReverse transcription polymerase chain reaction

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