Clinical significance of the BRAFV600E mutation in PTC and its effect on radioiodine therapy

Abstract

The goal of this study was to explore the relationship of the BRAFV600E mutation with clinicopathologic factors and evaluate the effect of radioactive iodine (RAI) therapy in a large group of intermediate- and high-risk papillary thyroid cancer (PTC) patients with the BRAFV600E mutation and without distant metastases. We collected data for PTC patients who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2014–December 2017. There were 1220 PTC patients who met the criteria, and the BRAFV600E mutation was observed in 979 of them (80.2%). Multivariate analysis identified that the BRAFV600E mutation remained independently associated with age at diagnosis, and bilaterality (OR = 1.023, 95% CI = 1.012–1.039, P < 0.001; OR = 1.685, 95% CI = 1.213–2.341, P = 0.002, respectively). In addition, the patients with bilateral PTCs had a higher prevalence of extrathyroid invasion, capsular invasion and fusion of metastatic lymph nodes than the unilateral PTC patients. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk; no significant difference was discerned between the BRAFV600E mutation and the wild-type groups (P = 0.237 and P = 0.498, respectively). To summarize, our results confirmed that PTC patients with the BRAFV600E mutation exhibit more aggressive characteristics. In addition, the patients with bilateral PTC have a higher incidence of extrathyroid invasion. Moreover, BRAFV600E mutation PTC patients did not show a poorer clinical response after postsurgical RAI therapy, suggesting that RAI therapy may improve the general clinical outcome of these patients.

Clinical Review: Navitoclax as a Pro-Apoptotic and Anti-Fibrotic Agent

“…BRAF V600E mutation in papillary thyroid cancer (PTC) highly corresponds to aggressive tumor features, including metastasis, cancer relapse, and failure of radioiodine treatment (Zhu et al, 2019). Vemurafenib, a potent BRAF inhibitor that exhibited FIGURE 4 | Mechanism of B-cell lymphoma-extra-large (BCL-X L ) inhibitor in diminishing liver fibrosis.…”

“…BRAF V600E mutation in papillary thyroid cancer (PTC) highly corresponds to aggressive tumor features, including metastasis, cancer relapse, and failure of radioiodine treatment ( Zhu et al, 2019 ). Vemurafenib, a potent BRAF inhibitor that exhibited strong efficiency in metastatic malignant melanoma possessing BRAF V600E mutation ( Mcarthur et al, 2014 ), also showed a convincing therapeutic effect against BRAFV600E-positive PTC ( Kim et al, 2013 ; Brose et al, 2016 ).…”

BRAF V600E and lymph node metastases in papillary thyroid cancer

“…In the current study, the BRAF V600E mutation was higher in the classical PTC subtype than in the other subtypes; however, the number of other subtypes were very small. A previous study done by our group, as well as the work of Sancisi et al , showed that the BRAF V600E mutation occurred less often in the invasive PTC subtype than in the classic subtype in PTC patients without distant metastases ( 8 , 27 ), and the prevalence of the BRAF V600E mutation was lower in follicular variant than in conventional PTC ( 28 ), although Straccia et al reported the opposite result ( 29 ). Criteria for inclusion and exclusion differed among the studies, which may have led to different results.…”

The Association Between Radioiodine Refractory in Papillary Thyroid Carcinoma, Sodium/Iodide Symporter Expression, and BRAFV600E Mutation

“… 15 Additionally, some studies have reported no association between the BRAF V600E mutation and radioiodine sensitivity in non-distant metastasis PTC groups. 34–37 …”