Urothelial cancer (UC) may be divided in two major subtypes, non-muscle invasive and muscle-invasive, with distinct biological and clinical properties. The majority of non-muscle-invasive tumors are papillary carcinomas (Ta) that do not invade the basal membrane, rarely metastasize, but have a high tendency to recur locally.
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. 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 procedures are unreliable for appropriate assessment.
To address this problem we have construct a molecular taxonomy of urothelial carcinoma i.e., the identification and description of molecular subtypes of UC by the combination of information on gene expression, epigenetic, genomic changes, and gene mutations. By this we have refined and optimized 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 is addressed from an integrated genomic perspective