Ventana Medical Systems, Inc., 1910 Innovation Park Drive, Tucson, AZ 85755, United States of America.
Penn Medicine at Chester County Hospital, Department of Pathology and Laboratory Medicine, 701 East Marshall Street, West Chester, PA 19380, United States of America.
Ann Diagn Pathol. 2020 Apr;45:151454. doi: 10.1016/j.anndiagpath.2019.151454. Epub 2019 Dec 14.
Lung cancer is the most common cancer worldwide and has the highest mortality rate. Carcinomas comprise 95% of all lung malignancies, the vast majority of which are non-small cell lung carcinomas (NSCLC). Increasingly, the diagnosis of lung cancer is established by examination of small tissue specimens obtained by minimally invasive techniques. It is critical to employ these tissues at maximum efficiency in order to render an accurate pathologic diagnosis and to perform theranostic studies, either genomic or by immunohistochemistry, to demonstrate genetic mutations that make patients eligible for molecularly targeted agents. Currently Thyroid Transcription Factor-1 (TTF-1) and Napsin A are the most commonly used immunohistochemical (IHC) stains to identify primary lung adenocarcinoma, and p40 and cytokeratin 5/6 (CK5/6) are used for squamous cell carcinoma. IHC stains for these markers, are performed either individually (IHC brown staining) or in combination as dual immunostains (i.e. TTF-1 + Napsin A and p40 + CK5/6, utilizing brown and red chromogens). Here we present a novel, truly multiplex immunohistochemical approach that combines staining with the above four antibodies on a single tissue section utilizing four different chromogens to accurately diagnose primary lung adenocarcinomas, squamous cell carcinomas, and combined adenosquamous carcinomas of the lung. Each marker is represented by a distinct color that can be read by a pathologist, using standard, bright field microscopy. We evaluated the ability of pathologists to differentiate NSCLCs using the multiplexed assay as compared to standard, single marker per slide diaminobenzidine (DAB)-based IHC. All cases in a cohort of 264 NSCLCs showed concordance of information (including positivity of stain, intensity of stain and coverage) between single IHC stains and the multiplex assay. This new multiplex IHC offers the capability to accurately diagnose and sub-classify primary lung NSCLCs, while conserving precious tissue for additional testing.
肺癌是全球最常见的癌症，也是死亡率最高的癌症。癌瘤占所有肺部恶性肿瘤的 95%，其中绝大多数是非小细胞肺癌（NSCLC）。越来越多的肺癌诊断是通过微创技术获得的小组织标本检查来确立的。为了做出准确的病理诊断，并进行治疗诊断研究，无论是基因组学还是免疫组织化学，以证明使患者有资格接受分子靶向药物治疗的基因突变，最大限度地利用这些组织至关重要。目前，甲状腺转录因子-1（TTF-1）和 Napsin A 是最常用的免疫组织化学（IHC）染色剂，用于识别原发性肺腺癌，而 p40 和细胞角蛋白 5/6（CK5/6）用于鳞状细胞癌。这些标志物的 IHC 染色剂，要么单独进行（IHC 棕色染色），要么作为双重免疫染色（即 TTF-1+Napsin A 和 p40+CK5/6，使用棕色和红色显色剂）进行。在这里，我们提出了一种新颖的、真正的多重免疫组织化学方法，即在单个组织切片上结合使用上述四种抗体进行染色，利用四种不同的显色剂来准确诊断原发性肺腺癌、鳞状细胞癌和肺的混合性腺鳞癌。每个标志物都由一种独特的颜色表示，可以由病理学家使用标准的明场显微镜进行读取。我们评估了病理学家使用多重检测与标准的单标记每幻灯片二氨基联苯胺（DAB）-基于 IHC 相比，区分 NSCLC 的能力。在 264 例 NSCLC 队列中，所有病例在单一 IHC 染色和多重检测之间的信息（包括染色的阳性、染色的强度和覆盖范围）均具有一致性。这种新的多重 IHC 提供了准确诊断和亚分类原发性肺 NSCLC 的能力，同时为进一步检测保存了珍贵的组织。
