Clinicopathological Features and Survival Analysis in Molecular Subtypes of Muscle-Invasive Bladder Cancer

Abstract

Molecular subtyping of bladder cancer (BC) aims to capture the biological heterogeneity of this complex disease in order to provide better patient risk stratification. Immunohistochemical (IHC) markers are regarded as promising surrogates to classify BCs into luminal and basal subtypes in routine practice. We investigated the correlation between the molecular subclassification, assessed through IHC, and the conventional prognostic variables of a cohort of 93 muscle-invasive BCs (MIBCs), with a focus on the pattern of muscularis propria (MP) invasion, and evaluated their association with outcome. Basal, luminal, double-positive (DP), and double-negative (DN) phenotypes were identified according to the coordinate expression of 1 basal (CK5/6) and 2 luminal (CK20, GATA3) markers, and accounted for 33.3%, 32.3%, 3.2%, and 31.2% (Scheme #1) and 9.7%, 60.2%, 26.9%, and 3.2% (Scheme #2). There was a significant association between the pattern of MP invasion and the molecular subtypes according to Scheme #2, in that all 8 basal and DN cases, as well as 83% of DP cases, had a non-infiltrative invasion pattern. No consistent differences were observed in terms of OS and CSS between the molecular subtypes obtained through surrogate IHC markers. In keeping with previous studies, we report the correlation between the identification of BC subtypes and the presence of morphological prognostic factors, supporting the need for a comprehensive pathological evaluation, including clinicopathological and molecular parameters, in order to improve the diagnosis and management of MIBC.