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Introduction <p>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.</p> Methods <p>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.</p> Results <p>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 (<i>p</i> &lt; 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%, <i>p</i> &lt; 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%, <i>p</i> &lt; 0.05).</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月25日

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  • Farhang Hooshmand,
  • Maral Mokhtari,
  • Shiva Aminnia,
  • Azin Dashtestani,
  • Ali Reza Rezvani,
  • Mohammadhossein Khorraminejad-Shirazi

摘要

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.