Clinicopathological and prognostic significance of programmed cell death ligand-1 expression in lung adenocarcinoma and its relationship with p53 status

Introduction: PD-L1 expression is a predictive biomarker for response to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors and can be evaluated by immunohistochemistry. Results of the clinicopathologic characteristics of PD-L1-positive lung adenocarcinoma have been inconsistent in previous studies, and there are no reports on the relationship between PD-L1 expression and p53 status in lung adenocarcinoma. Methods: We examined PD-L1 and p53 expression in a total of 323 surgically resected lung adenocarcinoma cases using anti-PD-L1 (clone SP142) and anti-p53 (clone DO-7) antibodies, and analyzed the clinicopathologic characteristics of PD-L1-positive cases and their relationship with p53 status. Results: PD-L1 expression in tumor cells was positive in 60 of 323 cases (18.6%). Higher PD-L1 expression (≥50%) was more prevalent in former or current smokers (p = 0.026) and was associated with more pack-years (p = 0.016). PD-L1-positive tumors were significantly associated with solid predominant type (p < 0.001), p53 aberrant expression (p < 0.001), and PD-L1 expression in tumor-infiltrating immune cells (p < 0.001). Patients with stage I to III tumors harboring PD-L1-positive tumor cells showed poor recurrence-free survival (p < 0.001) and overall survival (p < 0.001) on univariate analysis. Conclusions: PD-L1 expression in tumor cells, solid predominant histology, p53 aberrant expression, and PD-L1 expression in tumor-infiltrating immune cells are closely related. These variables should be considered when analyzing the clinical outcomes of patients with lung adenocarcinomas treated with anti-PD1/PD-L1 immune checkpoint inhibitors.