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.

Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours

“…The V600E BRAF mutation has been shown in approximately 43% of PTC (Lupi et al, 2007), ranging from 12% in PTC-FV to 77% in PTC-TCV (Xing, 2005). Interestingly, a distinct BRAF mutation (K601E) had been exclusively found in PTC-FV (Trovisco et al, , 2005 miRNA profiling in follicular thyroid tumours S-Y Sheu et al and in FA (Lima et al, 2004). The genetic and morphologic overlap of PTC-FV is also supported by the results of Castro et al (2006) who found similar frequencies of activating point mutations of the RAS genes and PAX8-PPARg rearrangement in PTC-FV, FA and FTC; both genetic alterations are absent (PAX8-PPARg; Kroll et al, 2000;Nikiforova et al, 2002) or exceedingly rarely (RAS; Vasko et al, 2003) found in 'non follicular variant' of PTC.…”

Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

“…The prevalence of the BRAF V600E mutation varies according to the histological subtype; the mutation is frequent in the tall cell variant and classic PTC, but absent in the cribriform-morular variant (Trovisco et al 2005). The clinical importance of the BRAF mutation derives from its role as a prognostic factor.…”

A High-Resolution Melting Protocol for Rapid and Accurate Differential Diagnosis of Thyroid Nodules

“…The main mutation of BRAF, identified exclusively in PTC, affects nucleotide 1799 in exon 15 and results in thymine-toadenine transversion, which translates into valine-to-glutamate substitution at residue 600 (p.V600E). 17 The adjacent p.K601E mutation has rarely been identified, 18 and no mutation in exon 11 has been described in thyroid cancers. BRAF mutations are associated with poor clinical prognosis due to extrathyroid invasion and higher risk of relapse and metastasis.…”