Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
ORIGINALS
Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia
Boban StanojevicRadan DzodicVladimir SaenkoZorka MilovanovicGordana PupicOgnjen ZivkovicIvan MarkovicIgor DjurisicMarko ButaBogomir DimitrijevicTatiana RogounovitchNorisato MitsutakeMariko MineYoshisada ShibataMasahiro NakashimaShunichi Yamashita
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2011 Volume 58 Issue 5 Pages 381-393

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Abstract

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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© The Japan Endocrine Society
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