Programmed Cell Death Ligand 1 Expression in Resected Non-Small Cell Lung Cancer.
Adenocarcinoma of Lung
/ genetics
Aged
B7-H1 Antigen
/ genetics
Carcinoma, Non-Small-Cell Lung
/ genetics
Cohort Studies
ErbB Receptors
/ genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ genetics
Male
Mutation
Neoplasm Staging
Norway
Prognosis
Proto-Oncogene Proteins p21(ras)
/ genetics
Sweden
Clinical correlations
NSCLC
PD-L1
Prognosis
Resected
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
08
04
2020
revised:
10
09
2020
accepted:
21
09
2020
pubmed:
21
11
2020
medline:
7
1
2022
entrez:
20
11
2020
Statut:
ppublish
Résumé
Recently, anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) immunotherapies have yielded promising outcomes for patients with advanced non-small cell lung cancer (NSCLC) and led to great interest in applying these agents to treat resectable early-stage NSCLC. The objective of our study was to evaluate PD-L1 protein expression in resectable early-stage NSCLC specimens from a large Northern European cohort, examine the relationship to clinical characteristics, and demonstrate the prognostic role in resected NSCLC. A large cohort of 875 NSCLC tumors consisted of 337 patients from Sweden and 538 patients from Norway was studied. All the patients had undergone pulmonary resection, and most patients had had early-stage NSCLC. PD-L1 protein expression was assessed by immunohistochemistry using the Dako PD-L1 22C3 pharmDx kit. The tumor proportion score for PD-L1 protein expression was compared with comprehensive demographic and clinicopathologic data. The overall prevalence of PD-L1 protein expression in the resectable NSCLC cohort was 9.5% at a tumor proportion score cutoff of ≥ 50%. Stage I NSCLC had lower PD-L1 expression compared with that of the other stages (P = .0012). PD-L1 expression correlated with wild-type EGFR gene expression (P = .0156) and mutated KRAS gene expression (P = .0004). No significant association was found between PD-L1 expression and mortality after multivariable adjustment for clinical characteristics, although the survival curves showed PD-L1 expression significantly correlated with a poor prognosis in the total NSCLC cohort and in the adenocarcinoma subgroup. PD-L1 expression in the present large cohort of resectable NSCLC was relatively low compared with data from clinical trials of advanced NSCLC. PD-L1 expression correlated positively with tumor stage, wild-type EGFR, and KRAS mutation. PD-L1 expression was not found as an independent prognostic factor in the present study. These findings could be important in the future when evaluating the role of anti-PD-1/PD-L1 immunotherapy in the setting of neoadjuvant or adjuvant trials for early-stage resectable NSCLC.
Sections du résumé
BACKGROUND
Recently, anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) immunotherapies have yielded promising outcomes for patients with advanced non-small cell lung cancer (NSCLC) and led to great interest in applying these agents to treat resectable early-stage NSCLC. The objective of our study was to evaluate PD-L1 protein expression in resectable early-stage NSCLC specimens from a large Northern European cohort, examine the relationship to clinical characteristics, and demonstrate the prognostic role in resected NSCLC.
MATERIALS AND METHODS
A large cohort of 875 NSCLC tumors consisted of 337 patients from Sweden and 538 patients from Norway was studied. All the patients had undergone pulmonary resection, and most patients had had early-stage NSCLC. PD-L1 protein expression was assessed by immunohistochemistry using the Dako PD-L1 22C3 pharmDx kit. The tumor proportion score for PD-L1 protein expression was compared with comprehensive demographic and clinicopathologic data.
RESULTS
The overall prevalence of PD-L1 protein expression in the resectable NSCLC cohort was 9.5% at a tumor proportion score cutoff of ≥ 50%. Stage I NSCLC had lower PD-L1 expression compared with that of the other stages (P = .0012). PD-L1 expression correlated with wild-type EGFR gene expression (P = .0156) and mutated KRAS gene expression (P = .0004). No significant association was found between PD-L1 expression and mortality after multivariable adjustment for clinical characteristics, although the survival curves showed PD-L1 expression significantly correlated with a poor prognosis in the total NSCLC cohort and in the adenocarcinoma subgroup.
CONCLUSION
PD-L1 expression in the present large cohort of resectable NSCLC was relatively low compared with data from clinical trials of advanced NSCLC. PD-L1 expression correlated positively with tumor stage, wild-type EGFR, and KRAS mutation. PD-L1 expression was not found as an independent prognostic factor in the present study. These findings could be important in the future when evaluating the role of anti-PD-1/PD-L1 immunotherapy in the setting of neoadjuvant or adjuvant trials for early-stage resectable NSCLC.
Identifiants
pubmed: 33214079
pii: S1525-7304(20)30299-0
doi: 10.1016/j.cllc.2020.09.018
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
KRAS protein, human
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e555-e562Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.