Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid:: A potential application for the preoperative assessment of thyroid nodules
Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid:: A potential application for the preoperative assessment of thyroid nodules
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DOI：
10.1158/1078-0432.ccr-03-0273
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发表时间：
2004-04-15
影响因子：
11.5
通讯作者：
Westra, WH
中科院分区：
文献类型：
--
作者：
Cohen, Y;Rosenbaum, E;Westra, WH
背景。细针抽吸（FNA）通常用于甲状腺结节的术前评估，但由于无法仅根据细胞学理由果断识别恶性肿瘤，因此后续的患者管理往往变得复杂。 BRAF 癌基因的激活突变通常发生在甲状腺乳头状癌 (PTC) 中，但不会发生在其他类型的良性和恶性甲状腺病变中。 FNA 的突变分析可以增强手术切除甲状腺结节的选择。方法：通过新开发的检测方法（使用新型引物延伸方法（MutectorR 检测）和直接测序）对 95 个切除的 PTC 以及 49 个相应的 FNA 进行 BRAF 突变评估。另外还对因怀疑恶性肿瘤而切除的甲状腺结节中的另外 42 个 FNA 进行了评估。结果：在 95 个切除的 PTC 中，有 36 个 (38%) 发现了 BRAF 突变。根据组织学亚型，BRAF 突变在传统 PTC 中比在滤泡型变异中更常见（67% 对比 12%；P < 0.0001；chi(2)）。术前 FNA 分析准确反映了 49 个配对样本中 46 个已切除 PTC 的 BRAF 状态（一致性为 94%）。在根据术前细胞学结果分组的 FNA 样本中（恶性，n = 25；良性，n = 11；不确定，n = 55），BRA F 突变证实了恶性组中 72% 的癌症为 PTC 诊断，并且不确定组中 16% 的癌症确诊为 PTC。 32 个良性甲状腺病变的 FNA 中未检测到 BRAF 突变。直接测序和MutectorR检测结果完全一致。结论：BRAF突变在传统PTC中很常见，并且是PTC特异的。可以在从甲状腺结节抽吸的细胞中可靠地检测到 BRAF 突变，表明该标记物在甲状腺结节术前评估中的作用。
Background. Fine needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules, but subsequent patient management is often complicated by the inability to decisively recognize malignancy on cytologic grounds alone. Activating mutations of the BRAF oncogene commonly occur in papillary thyroid carcinomas (PTCs) but not in other types of benign and malignant thyroid lesions. Mutational analysis of FNAs could enhance selection of thyroid nodules for surgical removal.Methods: Ninety-five excised PTCs along with 49 corresponding FNAs were evaluated for BRAF mutations by a newly developed assay that uses a novel primer extension method (MutectorR assay) and by direct sequencing. An additional 42 FNAs from thyroid nodules that were excised based on a suspicion of malignancy were also evaluated.Results: BRAF mutations were identified in 36 of the 95 (38%) excised PTCs. By histological subtype, BRAF mutations were more common in conventional PTCs than in the follicular variant (67% versus 12%; P < 0.0001; chi(2)). Analysis of the preoperative FNAs accurately reflected BRAF status of the resected PTC in 46 of the 49 paired samples (94% concordance). In FNA samples grouped according to the preoperative cytologic findings (malignant, n = 25; benign, n = 11; and indeterminate, n = 55), a BRA F mutation confirmed the diagnosis of PTC in 72% of carcinomas within the malignant group, and it established the diagnosis of PTC in 16% of carcinomas within the indeterminate group. BRAF mutations were not detected in FNAs from 32 benign thyroid lesions. Direct sequencing and the MutectorR assay yielded completely concordant results.Conclusions: BRAF mutations are common in conventional PTCs, and they are specific for PTC. A BRAF mutation can be reliably detected in cells aspirated from a thyroid nodule suggesting a role for this marker in the preoperative evaluation of thyroid nodules.