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PLoS One. 2018 Jun 1;13(6):e0198634. doi: 10.1371/journal.pone.0198634. eCollection 2018.

Clinicopathological analysis and prognostic significance of programmed cell death-ligand 1 protein and mRNA expression in non-small cell lung cancer.

Author information

1
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
2
Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
3
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Abstract

In this study, we present the clinicopathological features associated with PD-L1 protein and mRNA expression in a large Asian cohort of patients with non-small cell lung cancer (NSCLC) and assessed the prognostic implications of PD-L1 expression, particularly in early stage NSCLC. We retrospectively analyzed 687 NSCLC specimens (476 adenocarcinoma and 211 squamous cell carcinoma) using tissue microarray. PD-L1 immunohistochemistry (IHC) was performed using Dako 22C3 pharmDx assay and PDL1 mRNA was measured using RNA in situ hybridization (RISH). The overall prevalence of PD-L1 protein expression was 25.2% in tumor cells and PDL1 mRNA expression was 11.9%. There was a strong positive correlation between PD-L1 IHC and RISH results (Spearman's rho = 0.6, p<0.001). In adenocarcinoma, PD-L1 protein and mRNA expressions significantly correlated with poorly differentiated histologic subtype (p<0.001 and p = 0.002, respectively). PD-L1 expression was also associated with genetic alteration in adenocarcinoma. High PD-L1 expression level was associated with EGFR-naïve and KRAS-mutant subgroup (p = 0.001 and p = 0.017, respectively). With a 1% cut-off value, PD-L1 protein expression showed a short overall survival duration in early stage adenocarcinoma with marginal significance (p = 0.05, Hazard ratio = 1.947). Our study revealed that PD-L1 expression varied with histologic subtype and genomic alteration status in lung adenocarcinoma, and activation of the PD-L1 pathway may be a poor prognostic factor especially in early stage lung adenocarcinoma. In addition, PDL1 RISH showed promising results in predicting PD-L1 protein expression in NSCLC.

PMID:
29856861
PMCID:
PMC5983554
DOI:
10.1371/journal.pone.0198634
[Indexed for MEDLINE]
Free PMC Article

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