Predictive factors of outcome in poorly differentiated thyroid carcinomas

Eur J Cancer. 2018 Mar;92:40-47. doi: 10.1016/j.ejca.2017.12.027. Epub 2018 Feb 3.

Abstract

Background: The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis.

Methods: One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study. A pathological review was done for all cases (blinded to clinical data and outcome).

Results: All patients underwent thyroidectomy. Adjuvant radioactive-iodine was administered in 95.2% of them. Tumours were pT3 or pT4 in 68.3% of cases and metastatic in 38.5% of patients. Extrathyroidal extension (ETE) was observed in 40% of patients. At the end of the initial treatment, only 37% of patients were considered in remission. Fifty-two patients (50%) became refractory to radioiodine during follow-up. The 5-year overall survival was 72.8% and the 5-year recurrence-free survival (RFS) was 45.3%. Remission after initial treatment was an independent factor of RFS (HR = 0.22; [0.10-0.49]). ETE was the only significant parameter influencing the overall survival in multivariate analysis. TERT promoter mutations at positions -124 (C228T) and -146 (C250T) were present in 38.1% of analysed patients and significantly associated with radioiodine resistance but not with overall survival. Half of TERT promoter mutant tumours harboured also RAS or BRAF mutations.

Conclusion: PDTC form a heterogeneous group of patients with usual late-stage diagnosis, low radioactive iodine avidity and frequent metastatic spread. TERT promoter mutations could help to identify patients with high risk of radio-iodine refractoriness.

Keywords: Poorly differentiated thyroid carcinoma; RAI-resistant; RAS mutations; Recurrence risk; TERT promoter mutations.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinoma / genetics
  • Carcinoma / mortality
  • Carcinoma / secondary*
  • Carcinoma / surgery*
  • Cell Differentiation*
  • Child
  • Disease Progression
  • Disease-Free Survival
  • Female
  • France
  • Genes, ras
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Promoter Regions, Genetic
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics
  • Radiation Tolerance
  • Radiotherapy, Adjuvant
  • Risk Factors
  • Telomerase / genetics
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology*
  • Thyroid Neoplasms / surgery*
  • Thyroidectomy* / adverse effects
  • Thyroidectomy* / mortality
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase