PD-1 and PD-L1 expression in molecular subtypes of muscle-invasive bladder cancer: immunohistochemical characterization and correlation with clinicopathological features

Abstract

Introduction: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with variable outcomes, necessitating practical classification systems. Molecular subtyping using immunohistochemical (IHC) markers offers a cost-effective approach for therapeutic guidance and assessing survival. Moreover, MIBC molecular subclassification provides a practical approach for guiding immune checkpoint inhibitor therapy. Methods: We evaluated 124 MIBC cases using IHC markers GATA3, CK5/6, and p16. Cases were classified as luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), or other (GATA3-, CK5/6-). Luminal cases were further subdivided into luminal unstable (LumU; p16+) and luminal papillary (LumP; p16-). Clinicopathological characteristics of MIBC molecular subtypes were also assessed. PD-1 and PD-L1 expression were evaluated relative to clinicopathological features and MIBC subtypes. Results: In our study, 36.2% of the cases were LumU, 27.6% LumP, and 24.8% basal. The basal subtype generally shows a significantly higher tumor stage (p < 0.05). PD-1 was expressed in 70.5% of cases, with the highest expression in LumU (84.21%). PD-1 expression was significantly higher in the luminal compared to the basal subtype (82.1% vs. 53.8%, p < 0.01). PD-L1, expressed in 40% of cases, was significantly elevated in stage III and considerably higher in basal than luminal subtype (57.7% vs. 34.3%, p < 0.05). Conclusion: MIBCs were practically subclassified into LumU, LumP, basal, and other subtypes using three IHC markers. PD-1 expression was higher in the luminal subtype, while PD-L1 was predominantly elevated in the basal subtype. These findings highlight the potential of IHC-based subtyping to guide prognosis and treatment in MIBCs.