title: Meta-Analyses of Association Between BRAF(V600E) Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma.
abstract: OBJECTIVE
  The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shao-zheng
authors.initials: SZ
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yan-xing
authors.initials: YX
authors.lastname: Guan
authors.forename: Qing-jie
authors.initials: QJ
authors.lastname: Chen
authors.forename: Qin-yao
authors.initials: QY
authors.lastname: Zhu
mesh_terms: D000367:Age Factors; D002277:Carcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012737:Sex Factors; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf