An international interpretation study using the ALK IHC antibody D5F3 and a sensitive detection kit demonstrates high concordance between ALK IHC and ALK FISH and between evaluators.
An international interpretation study using the ALK IHC antibody D5F3 and a sensitive detection kit demonstrates high concordance between ALK IHC and ALK FISH and between evaluators.
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DOI：
10.1097/jto.0000000000000115
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发表时间：
2014-05
期刊：
影响因子：
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通讯作者：
Hirsch FR
中科院分区：
文献类型：
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作者：
Wynes MW;Sholl LM;Dietel M;Schuuring E;Tsao MS;Yatabe Y;Tubbs RR;Hirsch FR
个性化医疗的目标是根据肿瘤的分子特征，用预测有效的疗法治疗患者，从而使患者免于无效或有毒的治疗。间变性淋巴瘤激酶（ALK）抑制剂对ALK阳性非小细胞肺癌（NSCLC）肿瘤有效，但迄今为止唯一获批的伴随诊断是分离荧光原位杂交（FISH）测定。免疫组织化学（IHC）是一种临床适用的具有成本效益的检测方法，对ALK蛋白表达具有灵敏度和特异性。本研究的目的是组建一个国际病理学家专家团队，以评价一种新的自动化标准化ALK IHC检测试剂盒。既往通过FISH检测ALK重排的存档NSCLC肿瘤标本（n =103）由国际合作者提供。将这些标本通过用抗ALK（D5 F3）一抗与OptiView DAB IHC检测和OptiView扩增（Ventana Medical Systems，Inc.，Tucson，AZ）。如果肿瘤细胞中存在强烈的颗粒状细胞质棕色染色，则将标本分为阳性。将IHC结果与FISH结果进行了比较，并进行了评价者间比较。总体而言，对于100例可评价病例，ALK IHC检测试剂盒相对于ALK FISH结果具有高度敏感性（90%）、特异性（95%）和准确性（93%）。使用多数评分也观察到类似的结果。分别由7/7和6/7名评价者对3例和2例FISH阳性病例进行IHC阴性评分。七分之七的读片者对两例FISH阴性病例进行了免疫组化阳性评分。在审查前，七分之七的读者和七分之六的读者分别对88%和96%的病例达成一致，审查后，七分之七的读者和七分之六的读者分别对95%和97%的病例达成一致。根据专家评价，ALK IHC检测具有灵敏度、特异性和准确性，多名阅片人的多数评分不会使这些结果优于单个阅片人的评分。观察到良好的阅片人间一致性。这些数据支持ALK IHC在NSCLC评价中的算法使用。
The goal of personalized medicine is to treat patients with a therapy predicted to be efficacious based on the molecular characteristics of the tumor, thereby sparing the patient futile or toxic therapy. Anaplastic lymphoma kinase (ALK) inhibitors are effective against ALK-positive non–small-cell lung cancer (NSCLC) tumors, but to date the only approved companion diagnostic is a break-apart fluorescence in situ hybridization (FISH) assay. Immunohistochemistry (IHC) is a clinically applicable cost-effective test that is sensitive and specific for ALK protein expression. The purpose of this study was to assemble an international team of expert pathologists to evaluate a new automated standardized ALK IHC assay. Archival NSCLC tumor specimens (n =103) previously tested for ALK rearrangement by FISH were provided by the international collaborators. These specimens were stained by IHC with the anti-ALK (D5F3) primary antibody combined with OptiView DAB IHC detection and OptiView amplification (Ventana Medical Systems, Inc., Tucson, AZ). Specimens were scored binarily as positive if strong granular cytoplasmic brown staining was present in tumor cells. IHC results were compared with the FISH results and interevaluator comparisons made. Overall for the 100 evaluable cases the ALK IHC assay was highly sensitive (90%), specific (95%), and accurate relative (93%) to the ALK FISH results. Similar results were observed using a majority score. IHC negativity was scored by seven of seven and six of seven evaluators on three and two FISH-positive cases, respectively. IHC positivity was scored on two FISH-negative cases by seven of seven readers. There was agreement among seven of seven and six of seven readers on 88% and 96% of the cases before review, respectively, and after review there was agreement among seven of seven and six of seven on 95% and 97% of the cases, respectively. On the basis of expert evaluation the ALK IHC test is sensitive, specific, and accurate, and a majority score of multiple readers does not improve these results over an individual reader’s score. Excellent inter-reader agreement was observed. These data support the algorithmic use of ALK IHC in the evaluation of NSCLC.