Association of Lung Adenocarcinoma Subtypes According to the IASLC/ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells

Abstract

Background: Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features. Patients and Methods: PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival. Results: A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23-94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PD-L1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominant-papillary pattern, and 68.7% of patients with predominant-solid pattern (p = 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS. Conclusion: According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.

Keywords: NSCLC; Tumor-infiltrating lymphocytes (TILs) 4; immunohistochemistry; immunotherapy; lung adenocarcinoma; programmed-death receptor ligand 1 (PD-L1).