Brcic Luka, Savic Prince Spasenija
Diagnostik und Forschungsinstitut für Pathologie, Medizinische Universität Graz, Graz, Österreich.
Pathologie, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, Schönbeinstrasse 40, 4031, Basel, Schweiz.
Pathologe. 2022 May;43(3):222-228. doi: 10.1007/s00292-022-01066-4. Epub 2022 Apr 11.
Predictive immunochemistry is a time-, tumor sample- and cost-efficient method for testing the increasing number of predictive biomarkers in advanced non-small cell lung cancer (NSCLC). Immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded (FFPE) tumor tissue has an established role in detecting PD-L1 expression and in ALK, ROS1, and more recently NTRK testing. Cytology specimens as a source for predictive biomarker testing in NSCLC is very important as up to 40% of all NSCLC are diagnosed by cytology alone.Despite the established role of cytology in lung cancer diagnosis, no commercial IHC assays have been validated for cytology specimens.FFPE cell blocks (CB) are the most straightforward cytology preparation for predictive immunocytochemistry (ICC) as the results are valid using protocols standardized for FFPE histology. But CB are not always available.With non-CB cytology specimens being less standardized than FFPE histology and with considerable preanalytical variability, rigorous cytology-specific ICC protocol optimization, validation, and quality control are required. With this prerequisite, predictive ICC, most commonly performed on Papanicolaou-stained cytology specimens, is robust and reliable on non-CB preparations. This valuable material should not be underutilized for predictive biomarker testing, as this would put patients at risk of unnecessary repeat sampling. This review highlights preanalytical, analytical, and postanalytical aspects that may influence ICC results and summarizes the published data on predictive ICC for PD-L1, ALK, and ROS1 in NSCLC.
预测性免疫化学是一种高效省时、节省肿瘤样本且成本效益高的方法，可用于检测晚期非小细胞肺癌（NSCLC）中数量不断增加的预测性生物标志物。对福尔马林固定、石蜡包埋（FFPE）的肿瘤组织进行免疫组织化学（IHC）检测，在检测PD-L1表达以及ALK、ROS1检测，以及最近的NTRK检测中已确立了其作用。细胞学标本作为NSCLC预测性生物标志物检测的来源非常重要，因为所有NSCLC中高达40%仅通过细胞学诊断。尽管细胞学在肺癌诊断中已确立了作用，但尚无经验证的针对细胞学标本的商业IHC检测方法。FFPE细胞块（CB）是预测性免疫细胞化学（ICC）最直接的细胞学制备方法，因为使用针对FFPE组织学标准化的方案，结果是有效的。但CB并非总是可用。由于非CB细胞学标本不如FFPE组织学标准化，且存在相当大的分析前变异性，因此需要严格的针对细胞学的ICC方案优化、验证和质量控制。在此前提下，最常用于巴氏染色细胞学标本的预测性ICC在非CB制备上是稳健且可靠的。这种有价值的材料不应在预测性生物标志物检测中未得到充分利用，因为这会使患者面临不必要重复采样风险。本综述重点介绍了可能影响ICC结果的分析前、分析中和分析后方面，并总结了已发表的关于NSCLC中PD-L1、ALK和ROS1预测性ICC的数据。
