Diagnostic value of BRAF (V600E)-mutation analysis in fine-needle aspiration of thyroid nodules: a meta-analysis

Abstract

Fine-needle aspiration (FNA) is a reliable method for preoperative diagnosis of thyroid nodules; however, about 10%-40% nodules are classified as indeterminate. The BRAF (V600E) mutation is the most promising marker for thyroid FNA. This meta-analysis was conducted to investigate the diagnostic value of BRAF (V600E) analysis in thyroid FNA, especially the indeterminate cases. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, Elsevier, and the Cochrane Library databases for relevant studies prior to June 2015, and a total of 88 studies were ultimately included in this meta-analysis. Compared with FNA cytology, the synergism of BRAF (V600E) testing increased the diagnostic sensitivity from 81.4% to 87.4% and decreased the false-negative rate from 8% to 5.2%. In the indeterminate group, the mutation rate of BRAF (V600E) was 23% and varied in different subcategories (43.2% in suspicious for malignant cells [SMC], 13.77% in atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS], and 4.43% in follicular neoplasm/suspicious for follicular neoplasm [FN/SFN]). The sensitivity of BRAF (V600E) analysis was higher in SMC than that in AUS/FLUS and FN/SFN cases (59.4% vs 40.1% vs 19.5% respectively), while specificity was opposite (86.1% vs 99.5% vs 99.7% respectively). The areas under the summary receiver-operating characteristic curve also confirmed the diagnostic value of BRAF (V600E) testing in SMC and AUS/FLUS rather than FN/SFN cases. Therefore, BRAF (V600E) analysis can improve the diagnostic accuracy of thyroid FNA, especially indeterminate cases classified as SMC, and select malignancy to guide the extent of surgery.

Keywords: BRAFV600E mutation; fine-needle aspiration; meta-analysis; thyroid cancer.

Figure 1

Flowchart of study-selection process. Abbreviation: FNA, fine-needle aspiration.

Figure 2

Methodological quality of studies included, assessed by the Quality Assessment of Diagnostic Studies 2 criteria.

Figure 3

Summary receiver-operating characteristic (SROC) curve and area under the curve (AUC). Notes: FNA cytology (A), BRAF^V600E-mutation analysis (B), and combination of BRAF^V600E mutation and FNA cytology (C). *The Q index indicates the point at which sensitivity is equal to specificity. Abbreviations: FNA, fine-needle aspiration; SE, standard error.

Figure 4

Forest plots. Notes: Sensitivity (A), specificity (B), and summary receiver-operating characteristic (SROC) curve and area under the curve (AUC) (C) of BRAF^V600E-mutation analysis in cases classified as indeterminate by FNA cytology. *The Q index indicates the point at which sensitivity is equal to specificity. Abbreviations: FNA, fine-needle aspiration; CI, confidence interval; SE, standard error.

Figure 5

Summary receiver-operating characteristic (SROC) curve and area under the curve (AUC) of SMC cases (A), AUS/FLUS cases (B) and FN/SFN cases (C). Note: *The Q index indicates the point at which sensitivity is equal to specificity. Abbreviations: SMC, suspicious for malignant cells; AUS/FLUS, atypia of undetermined significance/follicular lesion of undetermined significance; FN/SFN, follicular neoplasm/suspicious for FN; SE, standard error.