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Abstract
We investigated the concordance of programmed death-ligand 1 (PD-L1) expression between primary cancer at initial diagnosis and metastasis at recurrence in resected non-small cell lung cancer (NSCLC). PD-L1 expression was evaluated using the SP142 assay in 37 NSCLC patients with paired primary lung cancer and surgically resected metastases at recurrence. PD-L1 positivity was defined as immunohistochemistry (IHC) and also evaluated by RNA in situ hybridization (RISH). The concordance rate of PD-L1 between primaries and metastases and correlation with clinicopathological factors were analyzed. PD-L1 expression was higher in squamous cell carcinoma, wild-type EGFR, and smokers than in non-squamous carcinoma, mutant EGFR, and never smokers, respectively. PD-L1 positivity was observed in 18.9% of primaries and 21.6% of metastases. IHC demonstrated 78.4% concordance of PD-L1 positivity between primary and metastatic cancers. In 10.8% of cases, PD-L1 positivity was higher in primaries than in metastases, and vice versa in the remaining 10.8%. By PD-L1 RISH, 35.1% of primaries and 27.0% of metastases demonstrated PD-L1 positivity. There was 62.2% concordance in PD-L1 by RISH between the primaries and metastases. Our results thus highlight the clinical importance of replacing metastases with primary archival tissue, particularly when re-biopsy is difficult at recurrence.
Highlights
Non-small cell lung cancers (NSCLCs) comprise nearly 80% of lung cancers and have a dismal prognosis, with an overall 5-year survival rate of only 15% [1].The treatment landscape of non-small cell lung cancer (NSCLC) has transformed with the approval of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade agents such as nivolumab, pembrolizumab, atezolizumab, and pembrolizumab in patients with ≥50% programmed death-ligand 1 (PD-L1) expression www.impactjournals.com/oncotarget as a front line of therapy [2,3,4,5,6,7]
High PD-L1 expression is used as a biomarker to predict the benefit from treatment with PD-1 signaling pathway inhibitors in NSCLC [16, 18]
We conducted this study to determine whether PD-L1 expression in primary lung cancer is concordant with that in metastatic lung cancer when recurrence occurs in NSCLC patients who have undergone curative resection
Summary
Non-small cell lung cancers (NSCLCs) comprise nearly 80% of lung cancers and have a dismal prognosis, with an overall 5-year survival rate of only 15% [1].The treatment landscape of NSCLC has transformed with the approval of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade agents such as nivolumab, pembrolizumab, atezolizumab, and pembrolizumab in patients with ≥50% PD-L1 expression www.impactjournals.com/oncotarget as a front line of therapy [2,3,4,5,6,7]. Non-small cell lung cancers (NSCLCs) comprise nearly 80% of lung cancers and have a dismal prognosis, with an overall 5-year survival rate of only 15% [1]. PD-1 is expressed on the surface of activated T cells [8]. PD-L1 interaction with PD-1 on T cells can induce the downregulation of T-cell function and enable tumor growth and persistence through immune evasion [8]. These immune checkpoint blockades have shown remarkable antitumor activity and long-duration response across a wide range of cancer types, including NSCLC [8]
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