Immunocytochemistry of cytology specimens for predictive biomarkers in lung cancer

With a growing number of predictive biomarkers that have emerged in non-small cell lung carcinoma (NSCLC), there has been a paradigm shift in the management of these patients. Of the various predictive biomarker testing methods, immunohistochemistry (IHC) is the most widely available, cost-effective, and commonly used methods. However, most predictive IHC assays are validated primarily on formalin-fixed paraffin-embedded (FFPE) histologic tissue samples and translating these assays to cytologic specimens requires additional and rigorous validation. This is part due to the lack of standardized processing protocols in cytology resulting in a variety of preanalytic variables that can impact the antigenicity of antibodies used for predictive biomarker testing. The review article discusses the various preanalytical and analytical factors that impact immunocytochemistry (ICC) in cytologic specimens and summarizes the current published literature on ALK, ROS1, PD-L1, and other predictive biomarker ICC in cytology.