Molecular Markers Are Associated with Onset of Radioiodine Refractoriness in Patients with Papillary Thyroid Carcinoma

J Nucl Med. 2023 Dec 1;64(12):1865-1868. doi: 10.2967/jnumed.123.266044.

Abstract

The onset of radioiodine-refractory thyroid carcinoma (RR-TC) is a negative predictor of survival and has been linked to the presence of BRAFV600E mutations in papillary thyroid cancer. We aimed to identify further genetic alterations associated with RR-TC. Methods: We included 38 patients with papillary thyroid cancer who underwent radioiodine imaging and 18F-FDG PET/CT after total thyroidectomy. The molecular profile was assessed by next-generation sequencing. The time to the onset of RR-TC for different genetic alterations was compared using the log-rank test. Results: The median onset to RR-TC was 0.7 and 19.8 mo in patients with and without, respectively, telomerase reverse transcriptase promoter mutations (P = 0.02) and 1.7 and 19.8 mo in patients with and without, respectively, a tumor protein 53 mutation (P < 0.01). This association was not observed for BRAFV600E mutations (P = 0.49). Conclusion: Our data show a significant association between the onset of RR-TC and mutations in telomerase reverse transcriptase promoter and tumor protein 53, indicating the need for a more extensive diagnostic workup in these patients. Certain genetic changes put patients with thyroid cancer at risk of developing cancer spread that does not respond to radioiodine therapy.

Keywords: TP53; molecular alterations; molecular imaging; papillary thyroid cancer; radioiodine refractoriness; radionuclide therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Carcinoma, Papillary*
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Mutation
  • Positron Emission Tomography Computed Tomography
  • Proto-Oncogene Proteins B-raf / genetics
  • Telomerase* / genetics
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / radiotherapy
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology
  • Thyroid Neoplasms* / radiotherapy

Substances

  • Iodine Radioisotopes
  • Telomerase
  • Proto-Oncogene Proteins B-raf
  • Biomarkers