title: Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma.
abstract: BACKGROUND
  Increased incidence of papillary thyroid carcinoma (PTC) is observed as a consequence of radiation exposure in connection to the Chornobyl nuclear plant accident in 1986. In this study, we report a cohort of adult Ukrainian patients diagnosed with PTC from 2004 to 2008 following exposure at the age of 18 years or younger.
  
  
  METHODS
  In total, 70 patients were identified and clinically characterized. The common BRAF 1799T>A mutation was assessed by pyrosequencing, the RET/PTC1 and RET/PTC3 (NCOA4) rearrangements by RT-PCR, and the expression of Ki-67 (MIB-1 index), BCL2, cyclin A, and cyclin D1 by immunohistochemistry.
  
  
  RESULTS
  In total, 46/70 (66%) cases carried a BRAF mutation and/or a RET/PTC rearrangement. A BRAF mutation was detected in 26 tumors, RET/PTC1 in 20 cases, and RET/PTC3 in four cases. In four of these cases, BRAF mutation and RET/PTC rearrangement were coexisting. The BRAF mutation was underrepresented among PTCs with accompanying chronic lymphocytic thyroiditis (CLT) compared with PTCs without this feature (12 vs 44%). MIB-1 proliferation index determined by double staining with leukocyte common antigen was low (mean 0.8%; range 0.05-4.5%). Moreover, increased expression of cyclin A was observed in PTCs with a tumor size >2 cm compared with PTCs ≤2 cm (1.2 vs 0.6%). BCL2 and cyclin D1 showed frequent expression but without associations to clinical characteristics or amplification of the CCND1 locus.
  
  
  CONCLUSIONS
  Our results suggest that this cohort has frequent BRAF mutation, RET/PTC1 rearrangement, and low proliferation index. Furthermore, BRAF 1799T>A was underrepresented in PTCs with CLT, and cyclin A expression was associated with increased PTC tumor size.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet. andrii.dinets@ki.se
authors.forename: Andrii
authors.initials: A
authors.lastname: Dinets
authors.forename: Mykola
authors.initials: M
authors.lastname: Hulchiy
authors.forename: Anastasios
authors.initials: A
authors.lastname: Sofiadis
authors.forename: Mehran
authors.initials: M
authors.lastname: Ghaderi
authors.forename: Anders
authors.initials: A
authors.lastname: Höög
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Jan
authors.initials: J
authors.lastname: Zedenius
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D047852:Chernobyl Nuclear Accident; D015331:Cohort Studies; D019925:Cyclin A / Q000032:analysis; D019938:Cyclin D1 / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000737:chemistry* / Q000209:etiology / Q000235:genetics*; D056918:Nuclear Receptor Coactivators / Q000235:genetics*; D000072079:Patched Receptors; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014586:USSR; D014455:Ukraine / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D019925:Cyclin A; D019394:Ki-67 Antigen; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D000072079:Patched Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D019938:Cyclin D1; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf