Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort

Br J Cancer. 2015 Dec 1;113(11):1556-64. doi: 10.1038/bjc.2015.372. Epub 2015 Dec 3.

Abstract

Background: There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.

Methods: This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13,243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were <18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression.

Results: We identified a borderline significant linear-quadratic association (P=0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements (P=0.020) or tumours with BRAF or RAS point mutations (P=0.008). Controlling for age, there were significant time trends in decreasing tumour size (P<0.001), the extent of lymphatic/vascular invasion (P=0.005), and overall invasiveness (P=0.026).

Conclusions: We determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Blood Vessels / pathology
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology*
  • Carcinoma, Papillary / secondary
  • Chernobyl Nuclear Accident
  • Child
  • Child, Preschool
  • ETS Translocation Variant 6 Protein
  • Early Detection of Cancer
  • Female
  • Humans
  • Iodine Radioisotopes / toxicity*
  • Lymphatic Vessels / pathology
  • Male
  • Neoplasm Invasiveness
  • PAX8 Transcription Factor
  • PPAR gamma / genetics
  • Paired Box Transcription Factors / genetics
  • Point Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • Radiation Dosage
  • Radiation Exposure / adverse effects*
  • Receptor, trkC / genetics
  • Repressor Proteins / genetics
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Translocation, Genetic
  • Tumor Burden
  • Ukraine / ethnology
  • United States
  • Young Adult
  • ras Proteins / genetics

Substances

  • Iodine Radioisotopes
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • PPAR gamma
  • Paired Box Transcription Factors
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor, trkC
  • Proto-Oncogene Proteins B-raf
  • ras Proteins