title: Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort.
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.
authors.affiliation: Laboratory of Morphology of Endocrine System, State Institution 'V.P. Komisarenko Institute of Endocrinology and Metabolism of Academy of Medical Sciences of Ukraine', Vishegorodskaya Street 69, Kyiv 254114, Ukraine.
authors.forename: Tetiana I
authors.initials: TI
authors.lastname: Bogdanova
authors.affiliation: Laboratory of Morphology of Endocrine System, State Institution 'V.P. Komisarenko Institute of Endocrinology and Metabolism of Academy of Medical Sciences of Ukraine', Vishegorodskaya Street 69, Kyiv 254114, Ukraine.
authors.forename: Liudmyla Yu
authors.initials: LY
authors.lastname: Zurnadzhy
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, 3477 Euler Way, Pittsburgh, PA 15213, USA.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, 3477 Euler Way, Pittsburgh, PA 15213, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Leeman-Neill
authors.affiliation: Department of Fundamental and Applied Problems of Endocrinology, State Institution 'V.P. Komisarenko Institute of Endocrinology and Metabolism of Academy of Medical Sciences of Ukraine', Vishegorodskaya Street 69, Kyiv 254114, Ukraine.
authors.forename: Mykola D
authors.initials: MD
authors.lastname: Tronko
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9778, Bethesda, MD 20892-9778, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9778, Bethesda, MD 20892-9778, USA.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Mabuchi
authors.affiliation: Department of Dosimetry and Radiation Protection, State Institution 'National Research Center for Radiation Medicine of Academy of Medical Sciences of Ukraine', Melnikova Street 53, Kyiv 04050, Ukraine.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Likhtarov
authors.affiliation: Laboratory of Radiation Protection, State Institution 'National Research Centre for Radiation Medicine of Academy of Medical Sciences of Ukraine', Melnikova Street 53, Kyiv 04050, Ukraine.
authors.forename: Leonila M
authors.initials: LM
authors.lastname: Kovgan
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9778, Bethesda, MD 20892-9778, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Drozdovitch
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9778, Bethesda, MD 20892-9778, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Little
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9778, Bethesda, MD 20892-9778, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Hatch
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, 3333 California Street, San Francisco, CA 94118-1944, USA.
authors.forename: Lydia B
authors.initials: LB
authors.lastname: Zablotska
authors.affiliation: Department of Medical Consequences of the Chernobyl accident and International Cooperation, State Institution 'V.P. Komisarenko Institute of Endocrinology and Metabolism of Academy of Medical Sciences of Ukraine', Vishegorodskaya Street 69, Kyiv 254114, Ukraine.
authors.forename: Viktor M
authors.initials: VM
authors.lastname: Shpak
authors.affiliation: The Thyroid Center, Columbia University, 161 Fort Washington Avenue, New York, NY, 10032, USA.|Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McConnell
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9778, Bethesda, MD 20892-9778, USA.
authors.forename: Alina V
authors.initials: AV
authors.lastname: Brenner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001808:Blood Vessels / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D047852:Chernobyl Nuclear Accident; D002648:Child; D002675:Child, Preschool; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000633:toxicity*; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D011829:Radiation Dosage; D000069079:Radiation Exposure / Q000009:adverse effects*; D020812:Receptor, trkC / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014178:Translocation, Genetic; D047368:Tumor Burden; D014455:Ukraine / Q000208:ethnology; D014481:United States; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D007457:Iodine Radioisotopes; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D048493:Proto-Oncogene Proteins B-raf; D050783:Proto-Oncogene Proteins c-ets; D051096:Proto-Oncogene Proteins c-ret; D020812:Receptor, trkC; D012097:Repressor Proteins; D018631:ras Proteins; D000097764:ETS Translocation Variant 6 Protein; C083325:PAX8 protein, human; C099282:RET protein, human