Diagnostic Value of FNA‐BRAF Mutation Analysis in Papillary Thyroid Cancer: A Systematic Review and Meta‐analysis

Abstract

Objectives: Fine needle aspiration (FNA) with cytological analysis is an initial step in investigating thyroid nodules. We systematically reviewed the diagnostic value of adding B-type Raf kinase (BRAFV600E) gene mutation analysis to the conventional FNA in the diagnosis of papillary thyroid cancer (PTC). Methods: Studies reporting BRAFV600E mutation analysis following FNA for evaluation of thyroid nodules were identified through searching electronic databases (eg, MEDLINE, EMBASE) through 1948-2011, scanning reference lists of relevant studies, and contacting experts. Two independent reviewers screened literature results, abstracted data, and appraised study quality. Meta-analysis of sensitivity and specificity was performed using bivariate random effects models. Results: Forty-two studies met our inclusion criteria after screening 787 citations and 117 full-text articles. The included studies enrolled approximately 7,676 patients with 8,196 FNA samples evaluated for BRAFV600E mutation. Bivariate-pooled sensitivity and specificity results from 29 included studies that examined BRAFV600E mutation among cytologically confirmed PTC samples were 72.6% (95% confidence interval [CI] 66.1-78.3%) and 50.8% (95% CI; 32.3-69.1%), respectively. For samples that were diagnosed cytologically as suspicious for PTC, and confirmed by histology as PTC, bivariate-pooled sensitivity and specificity results were 52.1% (95% CI; 36.3-67.4%) and 85.3% (95% CI; 55.2-96.5%), respectively. Eleven studies reported non-diagnostic FNA samples. The pooled sensitivity and specificity results for these samples were 50.5% (95% Cl; 31-69.8%) and 92.9% (95% Cl; 74.2-98.3%), respectively. Conclusions: BRAFV600E mutation analysis is associated with increase specificity and moderate increase in the sensitivity of FNA in the diagnosis of papillary thyroid cancer.