Molecular Features of Divergent Differentiation and Histological Subtypes in Bladder Cancer

Urothelial carcinoma shows high morphological heterogeneity. Some specific histological features have been defined as divergent differentiation or histological subtypes of invasive urothelial carcinoma. The striking heterogeneity of morphological phenotypes may to some extent reflect an underlying diversity in molecular features. This chapter provides a current overview of the reported associations between histological subtypes of invasive urothelial carcinoma and molecular features, including genomic alterations, transcriptional programs, and molecular subtypes. While some histological subtypes show specific or enriched genomic alterations, others share common genomic profiles with conventional urothelial carcinoma. At the transcriptomic level, some histological subtypes or divergent differentiation is strongly associated with luminal or basal molecular subtypes or shows altered gene expression programs. In rare histological subtypes or divergent differentiation, molecular profiling studies are lacking. More comprehensive analyses of molecular features in the context of histological subtypes require additional studies in larger cohorts.