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Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort
Authors:Tetiana I Bogdanova  Liudmyla Yu Zurnadzhy  Yuri E Nikiforov  Rebecca J Leeman-Neill  Mykola D Tronko  Stephen Chanock  Kiyohiko Mabuchi  Ilya A Likhtarov  Leonila M Kovgan  Vladimir Drozdovitch  Mark P Little  Maureen Hatch  Lydia B Zablotska  Viktor M Shpak  Robert J McConnell  Alina V Brenner
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.
Keywords:thyroid cancer   papillary thyroid carcinoma   radiation   iodine-131   pathology   Chernobyl   Chornobyl
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