原发性和转移性乳头状甲状腺癌中BRAF V600E突变的特异性免疫组化检测
Specific immunohistochemical detection of the BRAF V600E mutation in primary and metastatic papillary thyroid carcinoma.
作者信息
Zhu Xiaoli, Luo Yanli, Bai Qianming, Lu Yongming, Lu Yiqiong, Wu Lijing, Zhou Xiaoyan
机构信息
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Pathology, Shanghai Jiaotong University, Affiliated No. 6th People's Hospital, Shanghai 200233, China.
出版信息
Exp Mol Pathol. 2016 Feb;100(1):236-41. doi: 10.1016/j.yexmp.2016.01.004. Epub 2016 Jan 13.
PURPOSE
To evaluate the clinical value of immunohistochemistry (IHC) using anti-BRAF V600E antibody (clone VE1) for specific detection of the BRAF V600E mutant protein in formalin-fixed paraffin-embedded papillary thyroid carcinoma (PTC) specimens.
METHODS
A total of 118 PTC cases and 116 control cases processed between January 2008 and June 2010 were selected and created tissue microarrays (TMAs) for the study. BRAF V600E (VE1) IHC was performed on tissue sections from PTC cases to determine mutation status. Molecular tests (Sanger sequencing/ARMS) were used to confirm the BRAF V600E gene mutation in primary PTC.
RESULTS
A uniformly cytoplasmic staining throughout the tumors was observed in IHC-positive cases. BRAF V600E was detected in 68.6% (81/118) of PTC samples by IHC and in 61.9% (73/118) by Sanger sequencing/ARMS. The overall concordance between IHC and Sanger sequencing/ARMS was 93.2% (110/118). The sensitivity and specificity of the BRAF V600E IHC was 100% (73/73) and 82.2% (37/45), respectively. Positive and negative predictive values were 90.1% (73/81) and 100% (37/37), respectively. Expression of the BRAF V600E mutant protein was detected in all of 59 cases of primary carcinoma and corresponding metastatic carcinoma in lymph nodes. The concordance between IHC staining in primary and metastatic PTC was 100% (59/59).
CONCLUSION
IHC using VE1 antibody for detection of the BRAF V600E mutant protein expression in PTC showed high sensitivity and acceptable specificity, which are critical for diagnostic purposes. IHC staining for BRAF V600E showed uniformly cytoplasmic expression in both primary tumor and metastatic nodes. Therefore, IHC has high practical value for the detection of the BRAF V600E mutation in metastatic and primary PTC.
目的
评估使用抗BRAF V600E抗体（克隆号VE1）的免疫组织化学（IHC）在福尔马林固定石蜡包埋的甲状腺乳头状癌（PTC）标本中特异性检测BRAF V600E突变蛋白的临床价值。
方法
选取2008年1月至2010年6月间处理的118例PTC病例和116例对照病例，制作组织微阵列（TMA）用于研究。对PTC病例的组织切片进行BRAF V600E（VE1）免疫组化检测以确定突变状态。采用分子检测（桑格测序/扩增阻滞突变系统）来确认原发性PTC中的BRAF V600E基因突变。
结果
免疫组化阳性病例中可见肿瘤组织内均一的胞质染色。免疫组化检测发现118例PTC样本中有68.6%（81/118）存在BRAF V600E，桑格测序/扩增阻滞突变系统检测发现61.9%（73/118）存在该突变。免疫组化与桑格测序/扩增阻滞突变系统的总体一致性为93.2%（110/118）。BRAF V600E免疫组化的敏感性和特异性分别为100%（73/73）和82.2%（37/45）。阳性预测值和阴性预测值分别为90.1%（73/81）和100%（37/37）。在59例原发性癌及相应的淋巴结转移癌中均检测到BRAF V600E突变蛋白的表达。原发性和转移性PTC的免疫组化染色一致性为100%（59/59）。
结论
使用VE1抗体的免疫组化检测PTC中BRAF V600E突变蛋白表达具有高敏感性和可接受的特异性，这对诊断至关重要。BRAF V600E的免疫组化染色在原发性肿瘤和转移淋巴结中均显示均一的胞质表达。因此，免疫组化在检测转移性和原发性PTC中的BRAF V600E突变方面具有很高的实用价值。
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