Bladder cancer is a histologically and clinically heterogenous disease. Most bladder cancers are urothelial carcinomas, which frequently develop distinct histological subtypes. Several urothelial carcinoma histological subtypes, such as micropapillary, plasmacytoid, small-cell carcinoma and sarcomatoid, show highly aggressive behaviour and pose unique challenges in diagnosis and treatment. Comprehensive genomic characterizations of the urothelial carcinoma subtypes have revealed that they probably arise from a precursor subset of conventional urothelial carcinomas that belong to different molecular subtypes — micropapillary and plasmacytoid subtypes develop along the luminal pathway, whereas small-cell and sarcomatoid subtypes evolve along the basal pathway. The subtypes exhibit distinct genomic alterations, but in most cases their biological properties seem to be primarily determined by specific gene expression profiles, including epithelial–mesenchymal transition, urothelial-to-neural lineage plasticity, and immune infiltration with distinct upregulation of immune regulatory genes. These breakthrough studies have transformed our view of bladder cancer histological subtype biology, generated new hypotheses for therapy and chemoresistance, and facilitated the discovery of new therapeutic targets.

膀胱癌是一种组织学和临床异质性疾病。大多数膀胱癌是尿路上皮癌，经常形成不同的组织学亚型。几种尿路上皮癌组织学亚型，如微乳头状癌、浆细胞样癌、小细胞癌和肉瘤样癌，表现出高度侵袭性的行为，给诊断和治疗带来了独特的挑战。尿路上皮癌亚型的全面基因组特征表明，它们可能起源于属于不同分子亚型的传统尿路上皮癌的前体亚型——微乳头状和浆细胞样亚型沿着管腔途径发展，而小细胞和肉瘤样亚型沿着基底途径发展。途径。这些亚型表现出独特的基因组改变，但在大多数情况下，它们的生物学特性似乎主要由特定的基因表达谱决定，包括上皮-间质转化、尿路上皮-神经谱系可塑性，以及免疫调节基因明显上调的免疫浸润。这些突破性研究改变了我们对膀胱癌组织学亚型生物学的看法，提出了治疗和化疗耐药的新假设，并促进了新治疗靶点的发现。