Association with PD-L1 Expression and Clinicopathological Features in 1000 Lung Cancers: A Large Single-Institution Study of Surgically Resected Lung Cancers with a High Prevalence of EGFR Mutation

Abstract

Programmed cell death ligand 1 (PD-L1) expression is an important biomarker for predicting response to immunotherapy in clinical practice. Hence, identification and characterization of factors that predict high expression of PD-L1 in patients is critical. Various studies have reported the association of PD-L1 expression with driver genetic status in non-small cell cancer; however, the results have been conflicting and inconclusive. We analyzed the relationship between PD-L1 expression and clinicopathological factors including driver genetic alterations in 1000 resected lung cancers using a clinically validated PD-L1 immunohistochemical assay. PD-L1 expression was significantly higher in squamous cell carcinoma (SCC) compared to adenocarcinomas. PD-L1 expression in adenocarcinoma was associated with higher N-stage, solid histologic pattern, EGFR wild type, and ALK positive, but no significant association with the clinicopathological factors in SCC. EGFR mutant adenocarcinomas with distinctive clinicopathologic features, especially solid histologic pattern and higher stage showed higher PD-L1 expression. To the best of our knowledge, this study is the largest to evaluate the association between PD-L1 expression and clinicopathological and molecular features in lung cancer with a highly prevalent EGFR mutation. Therefore, our results are useful to guide the selection of lung cancer, even EGFR-mutated adenocarcinoma patients with PD-L1 expression, for further immunotherapy.

PD-L1 Immunohistochemistry Comparability and Their Correlation with Clinical Characteristics in NSCLC

“…In the current study, we found that PD-L1 expression was associated with a higher N stage, which is consistent with one report of 1000 resected lung cancers in Korea which showed that PD-L1 expression in adenocarcinoma was associated with a higher N stage, solid histologic pattern, EGFR wild type, and ALK mutation [ 26 ]. Interestingly, PD-L1 expression was associated with M0 rather than M1 stage ( p = 0.049), and a similar trend was found in our series.…”

“…Therefore, locally advanced lung cancer (higher N stage, M0, stage III) may have higher changes in PD-L1 expression than metastatic lung cancer (M1 stage, stage IV); however, the mechanism of tumor biology is unclear. In terms of genetic alterations, PD-L1 expression was associated with EGFR wild type and ALK mutations [ 26 , 27 ]. Similar trends were found in our series but did not reach statistical significance as limited cases are included in our study.…”

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC

“…Multiple studies have confirmed that PD‐L1 expression was associated with EGFR status 35,48,69–73 . Patients with EGFR mutations had decreased PD‐L1 expression according to a pool‐analysis of 15 public studies 28 .…”

“…While Shinchi Y et al 34 only detected a positive PD‐L1 expression rate of 26.8% in adenocarcinoma NSCLC. Two retrospective analyses also indicated a higher percentage of PD‐L1 expression in squamous than adenocarcinoma NSCLC (72.3% vs. 36.9% and 34.3% vs. 4.1%, respectively) 35,36 . The SP142 PD‐L1 IHC assay (Ventana) detected that the prevalence of PD‐L1 expression ranged from 50% to 55% in squamous NSCLC, 15,25,37–39 but was almost less than 40% in adenocarcinoma NSCLC 16,25,39 .…”

Good response with durvalumab after chemoradiotherapy for epidermal growth factor receptor exon 20 insertion adenocarcinoma: A case report

“…PD-L1 expression is recognized as a predictor of the ICI effect, and the TPS of PD-L1 of ≥50% in NSCLC has been reported to be 23.2% [ 10 ]. PD-L1 expression was significantly higher in patients with wild-type EGFR than those with EGFR mutations [ 11 ]. Cardona et al reported that 81.7% of patients with EGFR exon 20 insertions had TPS of PD-L1 of ≥1% expression [ 12 ].…”