Urothelial cancer (UC), bladder cancer, may be divided in two major subtypes, non-muscle invasive and muscle-invasive, that show very distinct biological and clinical properties. There are two forms of non muscle-invasive bladder cancer, the papillary carcinomas (Ta) that do not invade the basal membrane, rarely metastasize, but have a high tendency to recur locally, and the flat carcinoma in situ (CIS) that is a high risk lesion with a high tendency for invasion and metastasis. The T1 tumors are per definition “invasive” as they have penetrated the basal membrane, but they only extend into the lamina propria without any muscle engagement. Muscle invasive tumors are classified as T2-T4 depending on how deep the tumor has invaded the surrounding tissue. Non-muscle invasive tumors eventually progress to muscle-invasive tumors.
Prognosis and treatment decisions are mainly based on pathological criteria. As staging is reliant on tumor growth properties, proper staging is highly dependent on good quality biopsies. The fact that only 20-25% of high grade Ta tumors are confirmed by review pathology, and that 30% of patients with T1 tumors are upstaged after repeated transurethral resection (TUR), argues that standard TUR is an unreliable source for appropriate staging. Furthermore, even though tumor stage and grade has an impact on prognosis, progression, and treatment, more refined and optimized methods are in great need.
To address some of these problems we will construct a molecular taxonomy of urothelial cancer. With molecular taxonomy we mean the identification and description of molecular subtypes of UC by the combination of information on gene expression, epigenetic and genomic changes, and gene mutations. The overall goal is to refine and optimize UC classification into molecular subtypes important for prognosis and treatment. Furthermore, as data for all four biological levels will be assembled for a large set of tumors fundamental aspects of UC biology will be addressed from an integrated genomic perspective.