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.

Modifying factors of PD‐L1 expression on tumor cells in advanced non‐small‐cell lung cancer

“…Notably, <10% samples were categorized as PD‐L1 negative in the SOL pattern. These results align with previous findings in this population 17 …”

“…In this study, PD‐L1 expression was evaluated by two different assays (SP263 and 22C3), and distribution among different cut‐offs was in line with previous reports: negative and positive expression of PD‐L1 was observed in 44.4% and 55.6%. PD‐L1 high positive was identified in 14.0% of samples, which is in line with previous reports from INCan 17 . We found significantly more cases with PD‐L1 high expression whenever the chosen assay was SP263 (19.6%) and pathologists determined the PD‐L1 staining in the INCan samples (19.9%), which is an internal and academic setting.…”

“…PD‐L1 high positive was identified in 14.0% of samples, which is in line with previous reports from INCan. 17 We found significantly more cases with PD‐L1 high expression whenever the chosen assay was SP263 (19.6%) and pathologists determined the PD‐L1 staining in the INCan samples (19.9%), which is an internal and academic setting.…”

“…These results align with previous findings in this population. 17 The SOL predominant pattern has been associated with a higher tumor burden, higher copy number amplifications, higher fraction of genome altered, higher rate of wholegenome doubling, and higher number of oncogenic pathways altered than other ADC subtypes. 19 We hypothesized that the association between the SOL predominant ADC and the increased PD-L1 expression might be related to alterations in main oncogenic pathways (TP53, WNT, and MYC) which are usually impaired in this tumor subtype.…”

“…Numerical factors may influence variations in PD‐L1 expression reports, which may have significant consequences for clinicians in guiding treatment with ICIs. 8 , 16 , 17 This observational retrospective study evaluated, in a single cancer center, the PD‐L1 expression stratified in more relevant cut‐off points and associated them with the main clinicopathological and molecular characteristics in lung ADC specimens.…”