Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer

Assessment of programmed cell death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) is the definite diagnostic test to guide treatment for patients with advanced-stage non-small cell lung cancer. Intratumoral heterogeneity and discrepancy of PD-L1 expression between primary and metastatic lesions may increase the risk of tumor misclassification. We performed a retrospective study of the Foundation Medicine, Inc clinical database on lung cancer cases that were evaluated for PD-L1 expression by IHC in the context of routine care. All cases were assessed with the Food and Drug Administration-approved 22C3 pharmDx assay and scoring system. 15,028 lung cancer cases, including 8285 primary tumors and 6743 unmatched metastatic lesions were analyzed. Metastatic lesions (mets) were more frequently high positive (tumor proportion score (TPS) ≥50%) for PD-L1 expression than primary lesions (33.8% vs 28.4%; OR, 1.28; 95% CI, 1.19 to 1.37; p<0.001). Higher levels in mets than primaries were seen in samples from lymph nodes, pleural fluid, soft tissue and adrenal gland but not in those from liver, brain and bone. Metastatic lesions of patients with non-squamous histology were more likely to have TPS ≥50% in comparison with primary (OR, 1.37; 95% CI, 1.27 to 1.49; p<0.001), but this was not the case for patients with squamous histology (OR, 0.89; 95% CI, 0.74 to 1.06; p=0.197). PD-L1 expression varies with respect to histologic subtype, sampling site and gender, but is generally higher in metastatic sites. This observation may affect future patient management and trial design.