PD-L1 (22C3) Expression Correlates with Clinical and Molecular Features of Lung Adenocarcinomas in Cytological Samples

Introduction: PD-L1 expression is the most widely used predictive marker for immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. However, the current understanding of the association between PD-L1 expression and treatment response is suboptimal. A significant percentage of patients have only a cytological specimen available for clinical management. Therefore, it is relevant to examine the impact of molecular features on PD-L1 expression in cytological samples and how it might correlate with a therapeutic response. Methods: We evaluated patients diagnosed with adenocarcinoma of the lung who had both in-house targeted next-generation sequencing analysis and paired PD-L1 (22C3) immunohistochemical staining performed on the same cell blocks. We explored the association between molecular features and PD-L1 expression. In patients who underwent ICIs therapy, we assessed how a specific gene mutation impacted a therapeutic response. Results: 145 patients with lung adenocarcinoma were included in this study. PD-L1-high expression was found to be more common in pleural fluid than in other sample sites. Regional lymph node samples showed a higher proportion of PD-L1-high expression (29%) compared with lung samples (6%). The predictive value of PD-L1 expression was retained in cytological samples. Mutations in KRAS were also associated with a PD-L1-high expression. However, tumors with TP53 or KRAS mutations showed a lower therapy response rate regardless of the PD-L1 expression. Conclusion: Cytological samples maintain a predictive value for PD-L1 expression in patients with lung adenocarcinoma as regards the benefit of ICI treatment. Specific molecular alterations additionally impact PD-L1 expression and its predictive value.