Molecular Subtypes of Bladder Cancer: Component Signatures and Potential Value in Clinical Decision-making

Bladder cancer may be classified into “molecular subtypes” based on gene expression. These are associated with treatment response and patient outcomes. The gene expression signatures that define these subtypes are diverse, including signatures of epithelial differentiation, stromal involvement, cell cycle activity, and immune cell infiltration. Multiple different systems are described. While earlier studies considered molecular subtypes to be intrinsic properties of cancer, recent data have shown molecular subtypes change as tumors progress and evolve, and often differ between histologically distinct regions of a tumor. The data also indicate that some signatures that define molecular subtypes may be treated as independent continuous variables, rather than categorical subtypes, and these individual signatures may be more clinically informative. This review describes molecular subtypes of urothelial carcinoma, including histologic subtypes and tumors with divergent differentiation, and explores potential future uses in patient management.