Programmed cell death protein 1 and programmed death ligand 1 expression in neuroendocrine carcinomas of the urinary bladder

Abstract

Neuroendocrine carcinomas (NECs) of the urinary bladder are rare and aggressive, without an effective treatment approach. Immune checkpoint inhibitor agents targeting the interaction of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have been approved for urothelial carcinoma, but their use for small-cell carcinoma (SmCC) of the urinary bladder is unclear. Thus, we analyzed PD-1 and PD-L1 expression in NECs, particularly in SmCC of the urinary bladder. We used PD-1 antibody and two different biomarkers for PD-L1 antibodies, Ventana SP263 (Ventana Medical Systems, Inc.) and AM26531AF-N (Acris Antibodies GmbH). Among the 12 SmCC cases, 16.7% stained positive on immune cells for PD-1 and 33.0% for PD-L1. PD-L1 positivity on tumor cells was 25.0% of SmCC cases. The overall survival was shorter in PD-L1-positive patients compared with PD-L1-negative patients (15.4 months vs. 27.6 months). Large cell carcinoma (n = 1) was strongly and diffusely stained with PD-L1, and this case had the longest survival (68 months) in the group. Immune checkpoint inhibitors may be an alternative treatment option in SmCC of the urinary bladder. Furthermore, the absence of PD-L1 may be a good prognostic parameter.

Keywords

• immune checkpoint
• pd-1
• pd-l1
• small-cell carcinoma
• urinary bladder.