Molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely associated with mutational changes in the
BRAF,
RAS family and
RET genes. Our aim was to assess clinico-pathological and prognostic correlations of these PTC-specific gene alterations, with a particular emphasis on the
BRAF mutation, in a group of 266 Serbian PTC patients, for the first time. The reference center-based retrospective cohort included 201 (75.6%) females and 65 (24.4%) males aged 48.0±16.1 years (8-83 years old, range) diagnosed and treated for PTC during 1993-2008. Follow-up period was 53.1±41.6 months (7-187 months, range).
BRAF and
RAS mutations were determined by direct sequencing of genomic DNA.
RET/PTC rearrangements were analyzed by RT-PCR/Southern blotting. Genetic alterations were detected in 150/266 tumors (56.4%). One tumor displayed two genetic alterations. The
BRAFV600E was found in 84/266 (31.6%) cases,
RAS mutations in 11/266 (4.1%) and
RET/PTC in 55/266 (20.7%; 42/266 (15.8%)
RET/PTC1 and 13/266 (4.9%)
RET/PTC3). On multivariate analysis
BRAFV600E was associated with the classical papillary morphology (
P = 0.05), the higher pT category (
P = 0.05) and advanced clinical stage (
P = 0.03). In a proportional hazard model,
BRAFV600E did not appear to be an independent risk factor for the faster recurrence (
P = 0.784). We conclude that under the extensive thyroid surgery and limited application of radioiodine ablation
BRAFV600E may not be an indicator of poorer disease-free survival during the short to middle follow-up period. However, it has a potential to contribute to patients stratification into high- and low-risk groups.
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