Thyroid Fellow, University of Toronto, Toronto, Canada.
Toronto General Hospital, 200 Elizabeth Street, 12 EN-212, Toronto, Ontario, M5G 2C, Canada.
Endocr Pathol. 2019 Sep;30(3):201-218. doi: 10.1007/s12022-019-09585-2.
Immunohistochemistry (IHC) in evaluating thyroid surgical specimens may facilitate diagnostic and prognostic evaluation, with potential therapeutic implications. We performed a systematic review and meta-analysis examining the analytic validity of IHC in detecting BRAFV600E mutations in thyroid cancer (primary or metastatic). We screened citations from three electronic databases (until December 20, 2018), supplemented by a hand search of authors' files and cross-references of reviews. Citations and full-text papers were independently reviewed in duplicate, and consensus was achieved on inclusion of papers. Two reviewers independently critically appraised and abstracted data from included papers. Random-effect meta-analyses were conducted for sensitivity and specificity estimates. We reviewed 1499 unique citations and 93 full-text articles. We included 1 systematic review and 30 original articles. The published review (from 2015) needed to be updated as there were multiple subsequent original studies. The pooled sensitivity of IHC in detecting a BRAFV600E mutation was 96.8% (95% confidence interval [CI] at 94.1%, 98.3%) (29 studies, including 2659 BRAFV600E mutant tumors). The IHC pooled specificity was 86.3% (95% CI 80.7%, 90.4%) (28 studies, including 1107 BRAFV600E wild-type specimens). These meta-analyses were subject to statistically significant heterogeneity, partly explained by antibody type (sensitivity and specificity) and tissue/tumor type (specificity). In conclusion, BRAF IHC is highly sensitive and reasonably specific in detecting the BRAFV600E mutation; however, there is some variability in analytic performance.
免疫组织化学(IHC)在评估甲状腺手术标本中可促进诊断和预后评估,并具有潜在的治疗意义。我们进行了一项系统评价和荟萃分析,研究了 IHC 在检测甲状腺癌(原发性或转移性)中 BRAFV600E 突变的分析有效性。我们筛选了三个电子数据库的引用(截至 2018 年 12 月 20 日),并通过作者文件的手工搜索和综述的交叉引用进行补充。引用和全文论文由两名审查员独立进行重复审查,并就纳入论文达成共识。两名审查员独立批判性地评估并从纳入的论文中提取数据。对敏感性和特异性估计进行了随机效应荟萃分析。我们审查了 1499 个独特的引文和 93 篇全文文章。我们纳入了 1 项系统评价和 30 项原始文章。由于有多项后续原始研究,因此需要更新 2015 年发表的综述。IHC 检测 BRAFV600E 突变的汇总敏感性为 96.8%(95%置信区间 [CI] 94.1%,98.3%)(29 项研究,包括 2659 例 BRAFV600E 突变肿瘤)。IHC 的汇总特异性为 86.3%(95% CI 80.7%,90.4%)(28 项研究,包括 1107 例 BRAFV600E 野生型标本)。这些荟萃分析存在统计学显著的异质性,部分原因是抗体类型(敏感性和特异性)和组织/肿瘤类型(特异性)。总之,BRAF IHC 在检测 BRAFV600E 突变方面具有高度的敏感性和相当的特异性;然而,分析性能存在一定的变异性。