Detection of BRAF p.V600E Mutations in Melanoma by Immunohistochemistry Has a Good Interobserver Reproducibility
Detection of BRAF p.V600E Mutations in Melanoma by Immunohistochemistry Has a Good Interobserver Reproducibility
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DOI：
10.5858/arpa.2013-0031-oa
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发表时间：
2014-01-01
影响因子：
4.6
通讯作者：
Emile, Jean-Francois
中科院分区：
文献类型：
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作者：
Marin, Cristi;Beauchet, Alain;Emile, Jean-Francois
背景。-评估BRAF p.V600E突变状态对于转移性黑色素瘤患者的治疗是必要的。最近报道了在几种肿瘤类型中通过免疫组织化学检测p.V600E突变。评价在黑色素瘤中通过免疫组织化学检测BRAF p.V600E的观察者间重现性。用VE 1抗体对67例转移性黑色素瘤进行免疫组化。在组织微阵列的数字图像虚拟载玻片上进行染色判读。p.V600E状态由来自3个欧洲实验室的7名病理学家确定，对其他解释和分子生物学结果设盲。黑色素瘤具有p.V600E（n = 30）、p.V600K（n = 4）、p.K601E（n = 1）、p.600- 601 delinsE（n = 1）或无突变的细胞是胞质和弥漫性的，并且对于每种情况，3个组织微阵列核心上的染色是相似的。在53例（79.1%）病例中，7位病理学家的诊断完全一致。观察者间重现性的一致性几乎完美（kappa = 0.81 [0.77-0.85]）。仅获得2个假阳性反应（0.9%）。特异性报告为100%的5名病理学家（其中两人以前接受过p.V600E解释培训），和97%的2名未经培训的病理学家。在黑色素瘤中通过免疫组织化学检测BRAF p.V600E突变具有良好的观察者间重现性。我们的研究结果表明，免疫组化可作为检测BRAF p.V600E突变的第一步，以确定黑色素瘤患者作为BRAF抑制剂的候选人。
Context.-Assessment of BRAF p.V600E mutational status has become necessary for treatment of patients with metastatic melanoma. Detection of p.V600E mutation by immunohistochemistry was recently reported in several tumor types.Objective.-To evaluate the interobserver reproducibility of BRAF p.V600E detection by immunohistochemistry in melanoma.Design.-Immunohistochemistry with VE1 antibody was performed on metastatic melanomas of 67 patients. Staining interpretation was performed on digital image virtual slides of tissue microarrays. The p.V600E status was determined by 7 pathologists from 3 European laboratories, blinded for other interpretations and for molecular biology results.Results.-Melanomas had p.V600E (n = 30), p.V600K (n = 4), p.K601E (n = 1), p.600-601delinsE (n = 1), or no mutated cells was cytoplasmic and diffuse, and for each case the staining on the 3 tissue microarray cores was similar. In 53 cases (79.1%) the 7 pathologists had perfect concordance. Agreement of interobserver reproducibility was almost perfect (kappa = 0.81 [0.77-0.85]). Only 2 false-positive responses (0.9%) were obtained. The specificities reported were 100% for 5 pathologists (two of whom previously trained for p.V600E interpretation), and 97% for 2 untrained pathologists.Conclusions.-Detection of BRAF p.V600E mutation by immunohistochemistry in melanomas has an excellent interobserver reproducibility. Our results suggest that immunohistochemistry could be used as a first step for detection of BRAF p.V600E mutation, to identify patients with melanoma as candidates for BRAF inhibitors.