Immunohistochemistry in Bladder Cancer: Diagnostic, Prognostic, and Molecular Subtyping Applications

Introduction: Immunohistochemistry (IHC) has evolved from a primarily diagnostic adjunct to a central component of precision oncology in bladder cancer. By bridging histomorphology with molecular characterisation, IHC contributes to diagnosis, prognostication, staging, and therapeutic decision-making. However, variability in marker selection, interpretation, and standardisation remains a challenge in routine practice. Aim: This chapter aims to provide a focused overview of the role of IHC in bladder cancer, addressing current gaps in consistent application while highlighting its diagnostic utility, prognostic and predictive significance, role in molecular subtyping, and integration with emerging technologies. Key Points: IHC facilitates accurate detection of carcinoma in situ, molecular luminal–basal subtyping, and refined staging using markers such as CK20, GATA3, CK5/6, and smoothelin. Prognostic markers, including Ki-67 and p53, and predictive biomarkers such as PD-L1 and HER2, demonstrate increasing clinical relevance, with reported diagnostic and prognostic accuracies supporting their use in selected settings. The integration of multi-marker panels, digital pathology, and molecular diagnostics enhances reproducibility and precision, though limitations related to inter-observer variability, assay standardisation, and evolving biomarker validation persist. Conclusion: IHC remains a cornerstone of bladder cancer pathology, underpinning diagnostic accuracy and therapeutic stratification. With ongoing innovations in biomarker discovery, artificial intelligence, and standardisation, IHC continues to evolve as a critical platform for translational and clinical application in urologic oncology.