CORRELATION BETWEEN BRAFV600E MUTATION AND CLINICAL AND PATHOLOGICAL FEATURES OF PAPILLARY THYROID CARCINOMAS IN THE CZECH REPUBLIC

Sykorova V.¹, Dvorakova S.¹, Vaclavikova E.¹, Ryska A.², Kodetova D.³, Astl J.⁴, Duskova J.⁵, Smutny S.⁶, Vlcek P.⁷, Bendlova B.¹

¹Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic, ²Department of Pathology, Faculty of Medicine and University Hospital, Charles University, Hradec Kralove, Czech Republic, ³Institute of Pathology and Molecular Medicine, 2nd Medical Faculty, Charles University, Prague, Czech Republic, ⁴Department of ENT and Head and Neck Surgery, 1st Medical Faculty, Charles University, Prague, Czech Republic, ⁵Institute of Pathology, 1st Medical Faculty, Charles University, Prague, Czech Republic, ⁶Department of Surgery, 2nd Medical Faculty, Charles University, Prague, Czech Republic, ⁷Department of Nuclear Medicine and Endocrinology, 2nd Medical Faculty, Charles University, Prague, Czech Republic

Abstract

Background and aims: Activating point mutations of the BRAF gene are the most common genetic alteration reported in papillary thyroid carcinomas (PTC). The aim of this study was to determine the frequency of the BRAFV600E mutation in PTC tumor tissues and to correlate it with various clinical and pathological characteristics and to investigate whether the Chernobyl nuclear accident has any impact on the incidence of BRAFV600E in PTCs in the Czech Republic.
Methods: DNAs were extracted from 227 PTCs, including 77 fresh frozen thyroid samples, 8 fine needle aspiration biopsies and 142 paraffin-embedded formalin-fixed samples. The presence of the BRAFV600E mutation was determined using the single strand conformation polymorphism (SSCP) method and verified by direct sequencing.
Results: The BRAFV600E mutation was detected in 81 of 227 PTCs (35.7 %). The presence of pathological variants of PTCs with vs. without BRAFV600E mutation significantly differed (Fisher?s exact test, P=0.014). BRAFV600E was much less frequent in the folllicular variant (16.7 %) and mixed follicular-classical variant (10 %) of PTCs compared to the classical PTCs (44.4 %). There was a tendency to higher age at diagnosis in patients with BRAF mutation. No statistically significant correlation of BRAFV600E mutation with other parameters of the patients: gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, angioinvasion and presence of node metastases was observed. Prevalence of BRAFV600E mutation before Chernobyl accident was significantly lower than after the accident (5.3 % vs. 38.5 %, respectively, P=0.002).
Conclusions: This study has shown that the BRAFV600E mutation is more frequently associated with classical papillary architecture and underrepresented in follicular and mixed variants of PTCs. This data suggest that the follicular variant of PTC differs genetically from classical PTC. Possible influence of the Chernobyl nuclear accident on incidence of BRAFV600E mutation was demonstrated. Supported by IGA MH CR NR/9165-3.