title: Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia.
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 BRAF(V600E) 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 BRAF(V600E) 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, BRAF(V600E) 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 BRAF(V600E) 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.
authors.affiliation: Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Boban
authors.initials: B
authors.lastname: Stanojevic
authors.forename: Radan
authors.initials: R
authors.lastname: Dzodic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.forename: Zorka
authors.initials: Z
authors.lastname: Milovanovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Pupic
authors.forename: Ognjen
authors.initials: O
authors.lastname: Zivkovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Markovic
authors.forename: Igor
authors.initials: I
authors.lastname: Djurisic
authors.forename: Marko
authors.initials: M
authors.lastname: Buta
authors.forename: Bogomir
authors.initials: B
authors.lastname: Dimitrijevic
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rogounovitch
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Mariko
authors.initials: M
authors.lastname: Mine
authors.forename: Yoshisada
authors.initials: Y
authors.lastname: Shibata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D055771:Serbia / Q000453:epidemiology; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins