PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma Subtypes

Abstract

Purpose: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including adenocarcinoma subtypes.

Methods: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3.

Results: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS).

Conclusion: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.

Keywords: early adenocarcinoma; immunohistochemistry; lung cancer; programmed cell death 1; programmed death-ligand 1; subtype.

Fig. 1. Representative photograph of PD-L1 expression and TPS. (A) TPS <1% (negative staining) ×10, (B) TPS 1 to 49% (weakly positive) ×10, and (C) TPS ≥50% (highly positive) ×10. TPS: tumor proportion scores; PD-L1: programmed death-ligand 1

Fig. 2. Kaplan–Meier curves showing OS and RFS. (A) Kaplan–Meier curves showing OS. Patients with tumors with negative PD-L1 expression had slightly longer survival compared to patients with tumors of positive PD-L1 expression. There was no significant difference by log-rank test (p = 0.195). (B) Kaplan–Meier curves showing patients with negative PD-L1 expression had significantly longer RFS compared to patients with positive PD-L1 expression (p = 0.0426). OS: overall survival; RFS: recurrence-free survival; PD-L1: programmed death-ligand 1