Abstract
In this study, we present the clinicopathological features associated with PD-L1 protein and mRNA expression in a large Asian cohort of patients with non-small cell lung cancer (NSCLC) and assessed the prognostic implications of PD-L1 expression, particularly in early stage NSCLC. We retrospectively analyzed 687 NSCLC specimens (476 adenocarcinoma and 211 squamous cell carcinoma) using tissue microarray. PD-L1 immunohistochemistry (IHC) was performed using Dako 22C3 pharmDx assay and PDL1 mRNA was measured using RNA in situ hybridization (RISH). The overall prevalence of PD-L1 protein expression was 25.2% in tumor cells and PDL1 mRNA expression was 11.9%. There was a strong positive correlation between PD-L1 IHC and RISH results (Spearman’s rho = 0.6, p<0.001). In adenocarcinoma, PD-L1 protein and mRNA expressions significantly correlated with poorly differentiated histologic subtype (p<0.001 and p = 0.002, respectively). PD-L1 expression was also associated with genetic alteration in adenocarcinoma. High PD-L1 expression level was associated with EGFR-naïve and KRAS-mutant subgroup (p = 0.001 and p = 0.017, respectively). With a 1% cut-off value, PD-L1 protein expression showed a short overall survival duration in early stage adenocarcinoma with marginal significance (p = 0.05, Hazard ratio = 1.947). Our study revealed that PD-L1 expression varied with histologic subtype and genomic alteration status in lung adenocarcinoma, and activation of the PD-L1 pathway may be a poor prognostic factor especially in early stage lung adenocarcinoma. In addition, PDL1 RISH showed promising results in predicting PD-L1 protein expression in NSCLC.
Highlights
Researchers have recently become interested in developing immunotherapies for the treatment of non-small cell lung cancer (NSCLC), monoclonal antibodies targeting the programmed cell death-1 (PD-1) receptor and its ligand (PD-L1) [1, 2]
We demonstrated that PD-L1 expression was significantly associated with histologic grade and genetic alteration status in lung ADC
We assessed PD-L1 mRNA expression and compared PD-L1 protein and mRNA expression; the results showed that PD-L1 mRNA was a potential surrogate marker, with a positive correlation with protein expression
Summary
Researchers have recently become interested in developing immunotherapies for the treatment of non-small cell lung cancer (NSCLC), monoclonal antibodies targeting the programmed cell death-1 (PD-1) receptor and its ligand (PD-L1) [1, 2]. PD-L1 expression in NSCLC role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have