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Diagnostic value of BRAFV600E-mutation analysis in fine-needle aspiration of thyroid nodules: a meta-analysis

Authors Su X, Jiang X, Xu X, Wang W, Teng X, Shao A, Teng L

Received 3 December 2015

Accepted for publication 4 February 2016

Published 27 April 2016 Volume 2016:9 Pages 2495—2509


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Daniele Santini

Xingyun Su,1 Xiaoxia Jiang,1 Xin Xu,1 Weibin Wang,1 Xiaodong Teng,2 Anwen Shao,3 Lisong Teng1

1Department of Surgical Oncology, 2Department of Pathology, First Affiliated Hospital, 3Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China

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 BRAFV600E mutation is the most promising marker for thyroid FNA. This meta-analysis was conducted to investigate the diagnostic value of BRAFV600E 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 BRAFV600E 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 BRAFV600E 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 BRAFV600E 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 BRAFV600E testing in SMC and AUS/FLUS rather than FN/SFN cases. Therefore, BRAFV600E 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: thyroid cancer, fine-needle aspiration, BRAFV600E mutation, meta-analysis

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