PD-L1 in Cytological Samples: A Review and a Practical Approach

Abstract

With a growing number of predictive biomarkers needed to manage patients with non-small cell lung cancer (NSCLC), there has been a paradigm shift in care and handling of diagnostic samples. Among the various testing methods, immunohistochemistry (IHC) is the most cost- effective and widely available. Furthermore, over the past decade immunotherapy has emerged as one of the most promising cancer treatments. In this scenario IHC is the most used testing method available for PDL-1/PD1 immunotherapy. Several monoclonal antibodies targeting programmed death 1 (PD-1)/programmed death ligand-1 (PD-L1) pathways have been integrated into standard-of-care treatments of a wide range of cancer types, once provided evidence of PD-L1 expression in tumor cells by immunohistochemistry (IHC). Since currently available PD-L1 assays have been developed on formalin-fixed paraffin embedded (FFPE) histological specimens, a growing body of research is being dedicated to confirm the feasibility of applying PDL-1 assays also to cytological samples. Albeit promising results have been reported, several important issues still need to be addressed. Among these are the type of cytological samples, pre-analytical issues, cyto-histological correlation, and inter-observer agreement. This review briefly summarizes the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.

Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer

“…Additionally, we found no obvious difference in tumour cell content between cytological sample types. In our cohort, PE specimens were fixed in formalin compared to first CytoLyt ® and then formalin for BB and BAL samples, but this is unlikely to be a contributing factor [18].…”

“…A significant part of NSCLC is diagnosed on cytological specimens [13][14][15]. The suitability of cytology for PD-L1 testing has been discussed [16][17][18], and the lack of comprehensive data and validation has prevented wide acceptance. PD-L1 expression in paired histological and cytological materials from NSCLC patients has been compared in several studies [19,20].…”

“…Both methodological and biological aspects should be taken into account when comparing histology and cytology. The choice of PD-L1 assay, platform, and cut-off for a positive staining may have an impact on PD-L1 results regardless of specimen type, while fixation and preparation, specimen cell content, sampling site, heterogeneous expression, and interobserver agreement may be different for histological and cytological specimens [16][17][18]. Additionally, there is a mixture of both histological (biopsies, resections, and tissue microarrays) and cytological specimens (fine-needle aspirations, bronchoalveolar lavage [BAL], bronchial brush [BB], and pleural effusions [PE], etc.…”

EGFR Status Assessment for Better Care of Early Stage Non-Small Cell Lung Carcinoma: What Is Changing in the Daily Practice of Pathologists?

“…The biomarkers can exceptionally be evaluated on cytological material in the absence of associated tissue biopsies. The number of tumor cells in cytological samples generally allows evaluation of the expression of PD-L1; however, this assessment has to be done in more than one hundred tumor cells, which is not possible in all cases [92][93][94].…”

Program death ligand‐1 immunocytochemistry in lung cancer cytological samples: A systematic review

“…In addition, there are numerous cytology studies that address pre-analytical (e.g., different fixatives), analytical (e. g., antibody clone, staining platforms, inter and intra-observer agreement, cytology-histology concordance) and post-analytical (e.g., clinical outcome) issues. [11][12][13][14][15][16] Although promising results have emerged, many important questions about this field still need to be addressed. This review summarizes the literature of PD-L1 immunostaining in lung cytological specimens and provides practical tips for optimizing PD-L1 analysis.…”