Diagnostic value of fine needle aspiration BRAFV600E mutation analysis in papillary thyroid cancer: a systematic review and meta-analysis
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Fine needle aspiration (FNA) with cytologic analysis is an initial step in diagnosing thyroid nodules that are suspicious for cancer. We systematically reviewed the test accuracy of B-type Raf kinase (BRAF(V600E)) gene mutation analysis plus conventional FNA in the diagnosis of papillary thyroid cancer. We identified studies reporting BRAF(V600E) mutation analysis after FNA for evaluation of thyroid nodules through searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, scanning reference lists of relevant studies, and contacting experts. Two independent reviewers screened literature results, abstracted data, and appraised study quality. When appropriate, bivariate and univariate random-effects meta-analyses of sensitivity and specificity were considered for all outcomes. Forty-seven studies met our inclusion criteria after screening 1560 citations and 169 full-text articles. The included studies enrolled approximately 16170 patients with 9924 FNA samples evaluated for BRAF(V600E) mutation. Univariate pooled sensitivity was 69% (95% confidence interval, 61%-76%) for papillary thyroid cancer. For thyroid nodules that were diagnosed cytologically as suspicious for papillary thyroid cancer, univariate pooled sensitivity using FNA and BRAF(V600E) results was 52% (95% confidence interval, 39%-64%). Despite its high specificity, our meta-analysis shows that BRAF(V600E) mutation analysis has a low sensitivity in diagnosing papillary thyroid cancer in thyroid nodules. The feasibility of this test as a single molecular tool is not well established, which indicates the need for well-designed prospective clinical studies.
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