title: Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients' age but not with tumour aggressiveness.
abstract: A high prevalence of the BRAF(V600E) somatic mutation was recently reported in several series of papillary thyroid carcinomas (PTC). This mutation appears to be particularly prevalent in PTC with a predominantly papillary architecture. Another BRAF mutation (K601E) was detected in a follicular adenoma and in some cases of the follicular variant of PTC. The few studies on record provided controversial data on the relationship between the occurrence of BRAF mutations and clinicopathologic parameters such as gender, age and tumour staging. In an attempt to clarify such controversies we decided to enlarge our previous series to 315 tumours or tumour-like lesions diagnosed in 280 patients, including a thorough analysis of several clinicopathologic features. The BRAF(V600E) mutation was exclusively detected in PTC with a papillary or mixed follicular/papillary architecture both of the conventional type (46%) and of other histotypes, such as microcarcinoma (43%), Warthin-like PTC (75%) and oncocytic variant of PTC (55%). The BRAF(K601E) mutation was detected in four of the 54 cases of the follicular variant of PTC (7%). The mean age of patients with conventional PTC harbouring BRAF(V600E) (46.7 years) was significantly higher (P<0.0001) than that of patients with conventional PTC without BRAF(V600E) (29.5 years). The BRAF (BRAF(V600E)) mutated PTC did not exhibit signs of higher aggressiveness (size, vascular invasion, extra-thyroid extension and nodal metastasis) and were in fact less often multicentric than PTC without the mutation.
authors.affiliation: IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), R. Roberto Frias s/n, 4200, Porto, Portugal.
authors.forename: Vítor
authors.initials: V
authors.lastname: Trovisco
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: Ana
authors.initials: A
authors.lastname: Preto
authors.forename: Inês Vieira
authors.initials: IV
authors.lastname: de Castro
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: Patrícia
authors.initials: P
authors.lastname: Castro
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: Tiago
authors.initials: T
authors.lastname: Botelho
authors.forename: Severina
authors.initials: S
authors.lastname: Moreira
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Meireles
authors.forename: João
authors.initials: J
authors.lastname: Magalhães
authors.forename: Alexander
authors.initials: A
authors.lastname: Abrosimov
authors.forename: José
authors.initials: J
authors.lastname: Cameselle-Teijeiro
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000367:Age Factors; D002291:Carcinoma, Papillary / Q000235:genetics*; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012737:Sex Factors; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf