Clinical significance of BRAF V600E mutation in 154 patients with thyroid nodules

Abstract

Abstract. The aim of the present study was to investigate the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) patients from eastern coastal China and to determine whether it is correlated with the clinicopathological features of PTCs with or without current Hashimoto thyroiditis (HT). The BRAF V600E mutation status was analyzed in 206 thyroid nodules of 154 patients undergoing thyroidectomy using polymerase chain reaction and bi-directional sequencing. Multivariate analysis was performed to investigate the association of the BRAF V600E mutation with clinicopathological features. Thyroid nodules were classified as PTC, nodular goiter (NG), adenomatoid nodule, adenoma and HT. The BRAF V600E mutation was observed in 61.5% of PTCs analyzed; it was also detected in one normal tissue adjacent to PTC and one NG. One patient exhibited double mutations in the BRAF gene; the BRAF V600E mutation in the PTC lesion and the BRAF K601E mutation in the contralateral NG lesion. Patients harboring the BRAF V600E mutation had higher thyroid stimulating hormone levels (2.453±1.464 vs. 1.966±1.296 mIU/l), a reduced occurrence of papillary thyroid microcarcinoma (55.0 vs. 88%), and a higher occurrence of lymph node metastasis (LNM; 42.5 vs. 16.0%) compared with those with wild-type BRAF (all P<0.05). Binary logistic regression analysis revealed that the BRAF V600E mutation was associated with LNM of PTC (hazard ratio, 5.051; 95% confidence interval, 1.068-23.893; P= 0.041). Conversely, no association was identified between the BRAF V600E mutation and HT (38.5 vs. 67.3%, χ 2 =3.656, P=0.056). Thus, in regional PTCs, the BRAF V600E mutation was prevalent, suggesting that it may be an early and phenotypically defining molecular event in PTC, and may represent an independent factor that predicts LNM.

The Genetics of Papillary Microcarcinomas of the Thyroid: Diagnostic and Prognostic Implications

“…Although histological composition of the series and inclusion criteria of the patients, together with geographic variation, may help to explain these differences, more studies are needed in order to clarify the reason behind these observations. Data available suggests a higher prevalence of the mutation in Korea [ 16 , 28 , 31 , 34 , 37 , 38 , 44 , 46 , 54 , 55 , 57 , 58 , 61 , 65 ] in comparison with Italy [ 25 , 26 , 30 , 36 , 39 - 42 , 49 , 59 , 63 ] and China [ 47 , 50 , 52 , 60 , 64 , 66 ] and in series with higher proportion of tall cell variant mPTC [ 62 ].…”

“…The comparison of BRAF mutation prevalence in mPTC and PTC yields conflicting results. Some authors did not find significant differences in the prevalence of BRAF mutational status between mPTC and PTC [ 16 , 34 , 35 , 37 , 38 ], whereas others observed a significantly higher rate of mutation in PTC [ 24 , 42 , 43 , 45 , 49 , 51 , 57 , 65 , 66 ]. Out of 10.000 mPTCs collected in this review, 5741 were positive for BRAF mutation, and the global prevalence of BRAF in mPTC (57.4%) is similar to the 51% (27.3% - 87.1%) reported in a recent meta-analysis comprising 30 studies on PTC [ 67 ].…”

“…BRAF V600E, in contrast with the aforementioned genetic alterations, was largely evaluated as a prognostic marker in mPTC. Eleven out of 27 papers on BRAF mutation did not establish a significant correlation between BRAF V600E and any of the clinico-pathologic features previously associated with poor outcome [ 24 , 28 , 29 , 31 , 35 - 37 , 44 , 58 , 61 , 66 ] (Table 3 ). Nevertheless, the majority of them (16/27) observed a significant association between BRAF and at least one of such characteristics (Table 3 ).…”

Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins

“…Data generated from proteomics analysis of the tissues led us to the speculation that the malignancy in the patient may have been due to BRAF V600E mutation that was initiated from prolonged H 2 O 2 insults attributed to the germ line TRH R118Q mutation. Whilst this may be the molecular basis for malignancy in patients with PTCb, different mechanisms, such as germ line or direct mutation of the BRAF gene ( Waltz et al, 2014 ; Yu et al, 2015 ), may have been implicated in those with PTCa.…”

In-depth characterization of miRNome in papillary thyroid cancer with BRAF V600E mutation

“…There was various type of BRAF mutations reported for malignant tumours including PTC such as BRAF V600E, BRAF V600D, BRAF V600Q, BRAF V600V and BRAF V600L [40,41] . For our study, we only focused on BRAF V600E mutation as it was the most common BRAF mutation in PTC, which comprised more than 90% of cases [42] . Many studies had demonstrated an association of this BRAF mutation with the aggressive clinicopathological characteristics of PTC such as extrathyroidal invasion, lymph node metastasis and recurrence of PTC [8,43] .…”