Journal
CLINICAL GENITOURINARY CANCER
Volume 14, Issue 2, Pages 183-187Publisher
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clgc.2015.12.002
Keywords
Bladder cancer; Checkpoint inhibitors; 5H1; PD-1; PD-L1
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Funding
- Faculty of Medicine, American University of Beirut, Lebanon
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The aim of this study was to establish the frequency of PD-L1 expression in muscle-invasive bladder cancer cystectomy specimens and associated lymph node metastasis using immunohistochemistry. PD-L1 was overexpressed in the tumor cells of 5/52 (9.6%) of cystectomy specimens in this cohort with 17/52 (32.7%) of cases showing PD-L1 overexpression in tumor-infiltrating immune cells. Discordance was observed between PD-L1 expression in lymph node metastasis and the primary tumor. Background: The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) have shown activity in several tumor types with preliminary data suggesting a relationship between PD-L1 expression and response. The aim of this study was to establish the frequency of PD-L1 expression in muscle-invasive bladder cancer and associated lymph node metastasis using immunohistochemistry and to investigate the feasibility of using PD-L1 expression as a biomarker to select patients for PDe1-directed therapy. Patients and Methods: Cases of radical cystectomy for muscle-invasive bladder cancer with no exposure to previous chemotherapy were identified and representative slides from archived paraffin-embedded blocks stained with antiePD-L1 antibody (5H1 clone) were identified. PD-L1 positivity was defined by a 5% expression threshold. Results: Fifty-two radical cystectomy specimens were reviewed. PD-L1 was overexpressed in the tumor cells of 5/52 (9.6%) of cystectomy specimens in this cohort with 17/52 (32.7%) of cases showing PD-L1 overexpression in tumor-infiltrating immune cells. Discordance was observed between PD-L1 expression in lymph node metastasis and the primary tumor. Conclusion: Standard assays for PD-L1 expression have yet to be established. The observation of discordance between PD-L1 expression in metastatic sites and primary tumors suggests that prospective biomarker studies should aim to acquire material immediately before treatment initiation rather than archived tissue from resected specimens that might not reflect the current immune-active microenvironment. (C) 2016 Elsevier Inc. All rights reserved.
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