Programmed death ligand 1 protein expression is positively correlated with the solid predominant subtype, high MIB-1 labeling index, and p53 expression and negatively correlated with epidermal growth factor receptor mutations in lung adenocarcinoma

Abstract

Programmed death ligand 1 (PD-L1) protein expression is a proposed predictive biomarker of immunotherapy; thus, identification of the clinicopathological and molecular characteristics associated with PD-L1 expression is important and necessary. We examined PD-L1 immunohistochemical expression and its relationships with the clinicopathological and molecular characteristics of patients with surgically resected nonsmall cell lung carcinoma. PD-L1 expression differed according to the histological subtype. Among 633 patients with adenocarcinoma, 523 (82.6%) had no PD-L1 expression, 78 (12.3%) low expression, and 32 (5.1%) high expression. PD-L1 expression was more common in men (p<0.001), in smokers (p=0.002), and in patients with a more advanced stage (p=0.002), the solid predominant subtype (p<0.001), no epidermal growth factor receptor(EGFR) mutations (p<0.001), a high MIB-1 labeling index (p<0.001), and positive p53 immunohistochemical expression (p<0.001). In a multivariate logistic regression analysis, the solid predominant subtype (odds ratio [OR]=4.92, 95% confidence interval [CI]: 2.72-8.89, p<0.001), no EGFR mutations (OR=2.27, 95% CI: 1.35-2.7, p=0.002), a high MIB-1 labeling index (OR=2.78, 95% CI: 1.72-4.55, p<0.001), and p53 positivity (OR=2.13, 95% CI: 1.34-4.36, p=0.042) were significantly and independently associated with PD-L1 expression. The combination of the solid predominant subtype with a high MIB-1 labeling index was strongly associated with positive expression of PD-L1. In the 193 patients with squamous cell carcinoma, 92 (47.7%) had no PD-L1 expression, 57 (29.5%) low expression, and 44 (22.8%) high expression. There were no significant correlations between PD-L1 expression and the evaluated clinicopathological or molecular characteristics of these patients. These results, indicating associations of PD-L1 with various clinicopathological or molecular characteristics in adenocarcinoma but not squamous cell carcinoma, may be useful for selecting patients with a good response to immune checkpoint inhibitors.