Relationship between BRAF V600E and clinical features in papillary thyroid carcinoma

Abstract

Objective To investigate the mutant status of BRAF gene and analyze its relationship to epidemiological risk factors and clinical outcomes among patients with papillary thyroid cancer (PTC) in the largest, single-institution Chinese cohort to date. Methods The medical records of 2048 PTC patients were reviewed in this retrospective study. Single-factor and multiple logistic regression analyses were applied to identify risk factors for BRAF V600E mutation. Survival outcomes including distant metastatic and persistent or recurrent PTC were examined, with a mean follow-up time of 23.4 (5–47) months. Results The BRAF V600E mutation was present in 83.7% of patients (1715 of 2048). Correlation was found between BRAF V600E mutation and several epidemiological features, including age, concomitant hypertension and Hashimoto thyroiditis (HT). For the clinicopathological features, BRAF V600E was significantly associated with bilateral multifocality (odds ratio (OR) 1.233, 95% confidence interval (CI) 1.063–1.431, P < 0.01) and less lateral lymph node metastases (OR 0.496, 95% CI 0.357–0.689, P < 0.01). Smaller tumor size and advanced disease stage were significant in single-factor analyses but became insignificant after multivariate adjustment. No association was found between BRAF V600E mutation and extrathyroidal invasion, distant metastatic and disease persistence or recurrence. Conclusion Part of epidemiological features are independent risk or protective factors for BRAF V600E mutation. The presence of BRAF V600E mutation is not an aggressive prognosis on poor clinical outcomes in PTC. However, the high prevalence of BRAF V600E may provide guidance for surgery strategy and opportunity for targeted treatment in recurrent and advanced stage disease.

BRAF V600E and lymph node metastases in papillary thyroid cancer

“…Other studies detected BRAF V600E mutations in primary tumors in 48.5–83.7% of PTC cases, and BRAF V600E mutation frequency has increased in recent years ( 4 , 6 , 17 , 18 ). The BRAF V600E positivity in the current study is similar to the previous reports both in primary tumors ( 19 , 20 ) and in LNM ( 21 , 22 ). Some studies ( 9 , 21 ) found high concordance of the genotype between primary tumors and LNM in BRAF V600E mutations.…”

“…First, a relatively small number of PTC patients from a single center were retrospectively analyzed, thus, there may be a selection bias in enrolled patients in our study. However, the BRAF V600E mutation frequency in the primary tumors in this study (81.5%) was similar to previous reports (83.7%) ( 19 , 20 ). Likewise, the BRAF V600E positivity in LNM was 78% in our study, which was similar to other studies (73.9, 81.0%) ( 21 , 22 ).…”

“…The BRAF V600E mutation has been reported to be associated with aggressive characteristics and poor prognosis in PTC ( 4 , 5 , 6 ); however, there are different opinions in the literature. Some studies have reported that the BRAF V600E mutation is not associated with more extensive or aggressive clinicopathological features (such as extrathyroidal invasion) and is not predictive of recurrence or survival in PTC ( 19 , 31 , 32 , 34 , 35 , 36 ). In fact, the BRAF V600E mutation frequency in primary tumors and LNM was lower in PTC patients with distant metastases than in patients without distant metastases in our study, which was similar to the results of previous studies that suggested that the BRAF V600E mutation did not confer a metastatic advance to cancer cells ( 8 , 9 ).…”

Evaluation of the expression levels of BRAFV600E mRNA in primary tumors of thyroid cancer using an ultrasensitive mutation assay

“…The mRNA-based mutation detection assay, thus contributed to a 28% improvement in the sensitivity of detection, whereas the specificity of both the mRNA-and DNA-based assays was 100%. According to a number of studies, the prognostic relevance of BRAF V600E mutation still remains controversial in papillary thyroid carcinoma [23][24][25][26]. While the BRAF V600E mutation is not an independent predictor of poor outcome, the presence of the mutation is valuable for determining whether certain high-risk patients, in a relapse or primary metastatic setting, could be eligible for targeted BRAF inhibitor therapy with any of the currently available drugs, such as lenvatinib, vemurafenib or sorafenib [27].…”

Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

“…Classical subtype, characterized by a papillary and follicular variant, has an excellent prognosis, while patients with aggressive histopatholologic features in the primary tumor are considered at risk of developing RAI-refractory DTC [ 5 ]. BRAF V600E is the most common mutation observed in DTC and triggers tumorigenesis through the mitogen-activated protein kinase (MAPK) pathway [ 6 ]. Multiple studies have shown BRAF V600E mutation is associated with poor clinicopathologic outcomes, larger tumor size, local recurrence and distant metastases [ 7 , 8 ].…”