Pathogenesis of Urothelial Carcinoma

Abstract

The 2014 Cancer Genome Atlas Research Network study provided a significant update to the molecular understanding of urothelial carcinoma pathogenesis, recognizing four molecular subgroups of urothelial carcinoma: Cluster I (previously “luminal-type”), Cluster II (previously “p53-like”), and Clusters III and IV (previously “basal-type”). Cluster I encompasses low-grade urothelial carcinomas with papillary architecture and FGFR3 mutations, arising from the historical hyperplasia pathway. Cluster II encompasses high-grade urothelial carcinomas (HGUC) with a predominantly flat growth pattern and a high potential for muscle invasion, arising from the historical dysplasia pathway. Clusters III and IV are high-grade urothelial carcinomas with squamous or sarcomatoid morphology. The main goal of urinary tract cytology is the detection of urothelial neoplasms that have a high risk for invasion and metastasis; therefore, the main focus of The Paris System for Reporting Urinary Cytology is the detection of clinically significant urothelial neoplasia, namely HGUC.