Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma

Background: The clinicopathologic characteristics of tumors expressing programmed death (PD-1) ligands (PD-Ls) PD-L1 or PD-L2 and their associations with common driver mutations in lung adenocarcinoma are not clearly defined, despite the progression of anti-PD-1/PD-L1 immunotherapy.

Methods: PD-L1 and PD-L2 expression was measured by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinical variables, histologic subtypes, and the mutational status of EGFR, KRAS, HER2, and ALK.

Results: Positive PD-L1 expression was significantly associated with more advanced T status, N status, and pathologic stage. Histologically, lung adenocarcinomas with positive PD-L1 staining were less likely to be adenocarcinoma in situ or minimally invasive adenocarcinoma and more likely to have solid predominant subtype. Both PD-L1 expression (odds ratio =1.984, 95% confidence interval =1.010-3.894; P=0.047) and PD-L2 expression (odds ratio =2.328, 95% confidence interval =1.201-4.512; P=0.012) were independent predictors of poor overall survival. When the combined PD-L expression and pathologic stage were used together to predict overall survival, the concordance index increased to 0.763, and the Akaike information criteria value decreased to 356.08.

Conclusion: We defined the clinicopathologic features of lung adenocarcinomas with high expression of PD-L1 and PD-L2. We further demonstrated the role of PD-L expression as a useful prognostic marker for lung adenocarcinoma.