Molecular Subtype Profiling of Urothelial Carcinoma Using a Subtype-Specific Immunohistochemistry Panel

Molecular subtypes of bladder cancer (BC) can be determined by relatively small immunohistochemistry panels both for non-muscle invasive (NMI) and muscle invasive (MI) tumors. For analysis of NMI tumors, as few as two markers are needed, although classification is dependent also on pathological grade and histological evaluation. The result is a classification into the three tumor-cell phenotypes of NMI-BC, Urothelial-like (Uro), Genomically Unstable (GU), and Basal/SCC-like. For analysis of MI tumors, 13 markers are needed. The larger number of markers required for the classification of MI-BC reflects the inclusion of two additional phenotypes exclusively found in invasive tumors; Mesenchymal-like (Mes-like) and Small-cell/Neuroendocrine-like (Sc/NE-like). Here follows a description of how to perform and approach IHC-based subtype classification of bladder cancer.