1. Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma.
- Author
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Dinets A, Hulchiy M, Sofiadis A, Ghaderi M, Höög A, Larsson C, and Zedenius J
- Subjects
- Adult, Aged, Carcinoma, Papillary epidemiology, Carcinoma, Papillary etiology, Carcinoma, Papillary pathology, Cohort Studies, Cyclin A analysis, Cyclin D1 analysis, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Ki-67 Antigen analysis, Male, Middle Aged, Neoplasms, Radiation-Induced etiology, Patched Receptors, Phenotype, Proto-Oncogene Proteins c-bcl-2 analysis, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA methods, Thyroid Neoplasms epidemiology, Thyroid Neoplasms etiology, Thyroid Neoplasms pathology, USSR, Ukraine epidemiology, Up-Regulation, Biomarkers, Tumor analysis, Carcinoma, Papillary chemistry, Carcinoma, Papillary genetics, Chernobyl Nuclear Accident, Gene Rearrangement, Mutation, Neoplasms, Radiation-Induced chemistry, Neoplasms, Radiation-Induced genetics, Nuclear Receptor Coactivators genetics, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins c-ret genetics, Receptors, Cell Surface genetics, Thyroid Neoplasms chemistry, Thyroid Neoplasms genetics
- 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.
- Published
- 2012
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