Meta-Analyses of Association Between BRAF(V600E) Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma.

The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF(V600E) mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF(V600E) mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF(V600E) mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF(V600E) mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). This meta-analysis confirmed significant associations between BRAF(V600E) mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF(V600E) mutation for PTC prognosis.

Zhang Q ，Liu SZ ，Zhang Q ，Guan YX ，Chen QJ ，Zhu QY ... -  《-》

Clinicopathological Features and Prognosis of Papillary Thyroid Microcarcinoma for Surgery and Relationships with the BRAFV600E Mutational Status and Expression of Angiogenic Factors.

Shi C ，Guo Y ，Lv Y ，Nanding A ，Shi T ，Qin H ，He J ... -  《-》

BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis.

Li C ，Lee KC ，Schneider EB ，Zeiger MA ... -  《-》

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.

It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status.

Kim SK ，Woo JW ，Lee JH ，Park I ，Choe JH ，Kim JH ，Kim JS ... -  《-》

Correlation among the BRAF gene mutation status, clinicopathological features of primary tumour, and lymph node metastasizing of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant thyroid tumour. A common mutation of papillary thyroid carcinoma (PTC) is the somatic mutation of the BRAF (V600E) gene. The aim was to 1) determine the association of lymph node metastases of PTC with the BRAF gene mutation of primary tumour; 2) evaluate association of the BRAF mutation in the -primary tumour with clinicopathological para-meters; 3) examine the extent of genetic heterogeneity by monitoring the BRAF mutation in multicentric tumours. Retrospective analysis of the BRAF (V600E) mutation in PTC and PTC neck lymph node metastases in 156 patients operated from 2003 to 2012 in Prague and Zlín, the Czech Republic, using a qPCR assay. The results were correlated with clinicopathological factors. DNA was successfully extracted from 137 samples. The BRAF (V600E) mutation was detected in 78 cases (56.9%). The patients with BRAF p.Val600Glu mutation of primary tumour had only non-significantly higher risk of cervical lymph node metastases [OR=2.39 (95%) CI 1.00-5.75, p=0.052]. In the classic papillary variant, the BRAF (V600E) mutation was found significantly more often than in other PTC subtypes (p=0.022). We did not confirm any significant association between the BRAF (V600E) mutation and other clinicopathological findings. Except for the higher prevalence in papillary variant of PTC, BRAF p.Val600Glu mutation was not associated with other prognostic clinicopathological factors of PTC. BRAF mutation cannot be regarded as a reliable marker of node metastases in patients with PTC.

Lukas J ，Drabek J ，Dudesek B ，Vazan P ，Stranska J ，Jancik S ，Mackova M ，Syrucek M ，Lukas D ，Duskova J ，Dundr P ，Hintnausova B ，Jiskra J ... -  《-》