TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma

Eur J Cancer. 2019 Feb;108:41-49. doi: 10.1016/j.ejca.2018.12.003. Epub 2019 Jan 12.

Abstract

Background: TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer.

Patients: Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.

Results: The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients.

Conclusion: Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.

Keywords: Prognostic factors; TERT promoter mutations; Thyroid cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma, Follicular / genetics*
  • Adenocarcinoma, Follicular / pathology
  • Adenocarcinoma, Follicular / therapy
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • GTP Phosphohydrolases / genetics
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Radiotherapy, Adjuvant
  • Telomerase / genetics*
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Cancer, Papillary / therapy
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / therapy
  • Thyroidectomy
  • Young Adult

Substances

  • Iodine Radioisotopes
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase
  • GTP Phosphohydrolases
  • NRAS protein, human
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)