BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic.
BACKGROUND
Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics.


OBJECTIVE
Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters.


METHODS
DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing.


RESULTS
BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008).


CONCLUSIONS
Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.
Sykorova
V
V
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic. vlassyk@seznam.cz
Dvorakova
S
S
Ryska
A
A
Vcelak
J
J
Vaclavikova
E
E
Laco
J
J
Kodetova
D
D
Kodet
R
R
Cibula
A
A
Duskova
J
J
Hlobilkova
A
A
Astl
J
J
Vesely
D
D
Betka
J
J
Hoch
J
J
Smutny
S
S
Cap
J
J
Vlcek
P
P
Novak
Z
Z
Bendlova
B
B
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D047852:Chernobyl Nuclear Accident; D003062:Codon / Q000235:genetics; D018153:Czech Republic / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
D003062:Codon; D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf