The association of the BRAF^V600E mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer

Abstract

BACKGROUND:The effects of the BRAF V600E mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta-analysis to assess the strength of associations between these conditions and the BRAF V600E mutation. METHODS: The authors identified the clinical studies that examined the association of the BRAF V600E mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty-one relevant studies were hand-searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model. RESULTS: The average prevalence rate of the BRAF V600E mutation was 49.4%. In 26 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAF V600E mutation had increasedORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61-2.49). In 8 studies, patients with the mutation had 2.14-fold increased risk of recurrent and persistent disease (95% CI, 1.67-2.74). The associations were generally consistent across the different study populations. CONCLUSIONS: This meta-analysis demonstrates that the BRAF V600E mutation is closely related to the high-risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAF V600E mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients.

The synergic effect of BRAF^V600E mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

“…Besides, it is widely accepted that BRAF V600E mutation is an important independent factor on CLNM in PTCs [10,12,[20][21][22][23][24][25][26]. In this study, the incidence of BRAF V600E mutation was 50.6%, which was consistent with those in other studies.…”

RAC1b overexpression in papillary thyroid carcinoma: a role to unravel

“…The prognostic value of the BRAF V600E mutation in PTC patients has been an object of extensive studies. While many studies report an association of BRAF V600E mutation with a more aggressive behavior (13,16,17,20,22), others, including the present series, failed to document such association (14,18,19,21). These apparently conflicting results have to be reevaluated in light of a recent study (38) demonstrating that clonal occurrence of BRAF mutation is a rare event in PTC and that more frequently this mutation affects only a subpopulation of cells.…”

“…The V600E mutation constitutively activates BRAF kinase, leading to prolonged stimulation of the MAPK pathway, which ultimately leads to uncontrolled cell proliferation and faulty apoptosis (8,9,12). The majority of studies have associated BRAF V600E mutation with a more aggressive PTC behavior, whereas a few studies failed to reproduce this finding (13,14,15,16,17,18,19,20,21,22). Still, its value as a prognostic marker remains incompletely established and other players might be implicated, justifying the search for additional molecular markers.…”

Long-Term Prognosis of Differentiated Thyroid Cancer with Lung Metastasis in Korea and Its Prognostic Factors

“…In Korea, the incidence of thyroid cancer is also rapidly increasing; the incidence rates per 100,000 persons adjusting for age increased from 2.1 (in 1999) to 15.4 (in 2009) in males and 10.4 (in 1999) to 79.6 (in 2009) in females (23)-rates that are higher than in any other country studied (24). Furthermore, Korean DTCs have several distinguishing characteristics: (i) family history of DTC is twofold higher than in other studies (25), (ii) PTC is more frequent (more than 90%) (26), and (iii) DTC patients had higher rates of BRAF V600E mutations (58-81%) (27)(28)(29) in Korea than in any other country (30). Environmentally, Korea is one of the iodinesufficient areas in the world (31).…”