A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma

European Urology
Oliver PatschanMattias Höglund

Abstract

One third of patients with stage T1 urothelial carcinoma (UC) progress to muscle-invasive disease requiring radical surgery. Thus, reliable tools are needed for risk stratification of stage T1 UC. To investigate the extent to which stratification of stage T1 tumours into previously described molecular pathologic UC subtypes can provide improved information on tumour progression. A population-based cohort of 167 primary stage T1 UCs was characterised by immunohistochemistry and classified into the molecular subtypes urobasal (Uro, 32%), genomically unstable (GU, 58%), and squamous-cell-carcinoma-like (SCCL, 10%). Progression-free survival using univariate and multivariate models. Subtype classification was validated using nine additional markers with known subtype-specific expression. Analysis of mRNA expression of progression biomarkers revealed a strong association with molecular subtype. Kaplan-Meier analyses showed that the risk of progression was low for Uro tumours and high for GU/SCCL tumours. High progression risk scores were found only for GU/SCCL tumours. Clinical risk factors such as multifocality, concomitant carcinoma in situ, invasion depth, lymphovascular invasion, and high CD3(+) lymphocyte infiltration were obse...Continue Reading

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