Choden Sonam, Keelawat Somboon, Jung Chan Kwon, Bychkov Andrey
Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Cancers (Basel). 2020 Mar 5;12(3):596. doi: 10.3390/cancers12030596.
Detection of BRAF is useful for making diagnosis and risk stratification of papillary thyroid carcinoma (PTC). Molecular testing, however, is not always available for routine clinical use. To assess the clinical utility and reliability of VE1 immunohistochemistry (IHC) for detecting BRAF mutation in PTC, VE1 IHC was performed on the tissue microarrays of 514 patients with PTC and was compared with Sanger sequencing results. Of 514 PTC cases, 433 (84.2%) were positive for VE1 expression. Among 6 discordant cases between VE1 IHC and Sanger sequencing, 3 initial VE1-false negative cases turned out to be true false negative on repeat testing, and 3 VE1-false positive cases showed BRAF mutation using digital PCR analysis. PTCs with low variant allele fraction were positive for VE1 IHC but were not detected using sequencing. VE1 IHC showed 99.3% sensitivity, 100% specificity, 100% positive predictive value, and 96.4% negative predictive value. The BRAF mutation was significantly associated with older age, multifocality, extrathyroidal extension, lymph node metastasis, and advanced tumor stage. In conclusion, VE1 IHC is a reliable method for detecting BRAF mutation in PTC specimens.
检测BRAF对甲状腺乳头状癌（PTC）的诊断和风险分层具有重要意义。然而，分子检测并非总能用于常规临床应用。为评估VE1免疫组化（IHC）检测PTC中BRAF突变的临床实用性和可靠性，对514例PTC患者的组织芯片进行了VE1 IHC检测，并与桑格测序结果进行比较。在514例PTC病例中，433例（84.2%）VE1表达呈阳性。在VE1 IHC与桑格测序结果不一致的6例病例中，3例最初VE1假阴性病例在重复检测时被证实为真阴性，3例VE1假阳性病例经数字PCR分析显示存在BRAF突变。变异等位基因分数低的PTC病例VE1 IHC呈阳性，但测序未检测到。VE1 IHC的敏感性为99.3%，特异性为100%，阳性预测值为100%，阴性预测值为96.4%。BRAF突变与年龄较大、多灶性、甲状腺外侵犯、淋巴结转移及肿瘤晚期显著相关。总之，VE1 IHC是检测PTC标本中BRAF突变的可靠方法。
