[Predictive immunocytochemistry in non-small cell lung carcinoma]

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.