Diagnostic value of fine needle aspiration BRAFV600E mutation analysis in papillary thyroid cancer: a systematic review and meta-analysis

Abstract

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.

Clinical utility of immunohistochemistry using the novel anti-BRAF V600E antibody (clone RM8) for detection of the BRAF V600E mutant protein in papillary thyroid cancers

“…[19,20] It is therefore prudent that the treating clinician is aware of the various platforms for detection of mutant BRAF. A qPCR based mutant BRAF detection can be easily done on a wide variety of specimens including FNAC specimens from suspicious thyroid nodules, thus giving an additional diagnostic potential of this technology.…”

Molecular pathology and thyroid FNA

“…A meta‐analysis of 47 studies of BRAF V600E testing of FNA cytology specimens showed a pooled sensitivity for BRAF V600E testing in thyroid FNA of 52% (95% CI 39%‐64%). 36 Sensitivity when reported in individual studies was 100% but pooled sensitivity for indeterminate FNA (category III to V) in the six studies where this could be calculated was 31% (95% CI, 6%‐56%) . BRAF V600E testing is also useful because NIFTP tumours, which are follicular derived RAS ‐driven thyroid lesions, if strict diagnostic criteria are applied, rarely show BRAF V600E mutations and so the presence of a BRAF V600E mutation can be used to exclude a NIFTP tumour in FNA aspirates when nuclear features suggestive of papillary carcinoma are present.…”

Inhibitory roles of miR‑9 on papillary thyroid cancer through targeting BRAF

“…BRAF is a critical factor participating in the pathogenesis of thyroid cancer, and a high frequency of BRAF mutations has been detected among patients with PTC (40). Accumulating evidence suggests that a mutation in BRAF at the amino acid residue 600 (V600E) may be associated with the prognosis of patients with PTC (41)(42)(43). BRAF may be implicated in PTC progression through several signaling pathways, including the MEK/ERK and the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt pathway (44)(45)(46).…”