Laboratory of Clinical and Experimental Pathology/ Hospital-Integrated Biobank (BB-0033-00025), CHU Nice, FHU OncoAge, Université Côte d'Azur, Nice, France.
EMEA-LATAM division, Roche Diagnostics France, Meylan, France.
Lung Cancer. 2018 Oct;124:90-94. doi: 10.1016/j.lungcan.2018.07.037. Epub 2018 Jul 31.
The current challenge in the management of non-small cell lung cancer (NSCLC) in pathology laboratories is to combine immunohistochemistry (IHC) and molecular approaches on increasingly smaller biopsies and the need to reserve a fair amount of tumor material for molecular analyses with increasingly larger panels. The latest lung cancer classification, especially in the setting of poorly differentiated tumors, requires an IHC workup to allow for accurate diagnosis and also to preserve as much tissue as possible for molecular testing. Thus, it is recommended to reduce use of the term NSCLC not otherwise specified as much as possible and classify tumors according to their specific histologic subtype. This implies limiting the number of tissue slides despite the existence of specific and sensitive biomarkers (ALK, ROS1, BRAF V600E, PD-L1) and the obligation to distinguish lung adenocarcinoma (TTF-1 positive) from squamous cell carcinoma (p40 positive).
Samples from 18 patients with NSCLC, previously characterized for histologic and genomic/immune features, were included. Two multiplexed IHC assays were developed, for diagnosis and immunophenotyping including TTF1, p40, PD-L1, and pan-Keratin antibodies, and for molecular profiling panel including ALK, ROS1 and BRAF V600E antibodies.
We developed two sensitive multiplexed IHC assays to comprehensively characterize major NSCLC histotypes and FDA-cleared predictive biomarkers, without antigenicity loss, steric interference or increased cross-reactivity. The assays rely on standard antigen retrieval and automated staining protocols, limiting the need for validation strategies.
Our multiplexed IHC approach provides a unique sample-sparing tool to characterize limited tissue samples in lung oncology and making it an alternative method in the clinical setting for therapeutic decision making of advanced NSCLC, provided that validation in a larger population is performed.
目前，病理实验室在非小细胞肺癌（NSCLC）的管理上面临着一项挑战，即需要在不断减小的活检样本上结合免疫组织化学（IHC）和分子方法，并且需要为越来越大的面板保留相当数量的肿瘤材料进行分子分析。最新的肺癌分类，特别是在分化不良的肿瘤中，需要进行 IHC 检查，以便进行准确的诊断，并尽可能多地保留组织进行分子检测。因此，建议尽可能减少使用“非特指性 NSCLC”这一术语，并根据其特定的组织学亚型对肿瘤进行分类。这意味着尽管存在特定且敏感的生物标志物（ALK、ROS1、BRAF V600E、PD-L1），但仍需要限制组织切片的数量，并且有义务区分肺腺癌（TTF-1 阳性）和鳞状细胞癌（p40 阳性）。
纳入了 18 名 NSCLC 患者的样本，这些患者之前已通过组织学和基因组/免疫特征进行了特征描述。开发了两种多重免疫组织化学检测方法，一种用于诊断和免疫表型分析，包括 TTF1、p40、PD-L1 和泛角蛋白抗体，另一种用于分子分析面板，包括 ALK、ROS1 和 BRAF V600E 抗体。
我们开发了两种敏感的多重免疫组织化学检测方法，可全面描述主要的 NSCLC 组织学类型和 FDA 批准的预测性生物标志物，而不会导致抗原性丧失、空间干扰或增加交叉反应性。这些检测方法依赖于标准的抗原修复和自动化染色方案，限制了验证策略的需求。
我们的多重免疫组织化学方法提供了一种独特的样本节约工具，可用于对肺癌中的有限组织样本进行特征描述，并且在提供验证的情况下，在临床环境中也可以作为治疗晚期 NSCLC 的决策替代方法。
