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Molecular Subtypes of Bladder Cancer

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
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Abstract

Purpose of Review

Recent whole genome characterizations of primary human bladder cancers revealed that they can be grouped into “intrinsic” basal and luminal molecular subtypes. Here, we provide an overview of the subtypes and discuss their biological and clinical properties.

Recent Findings

Basal cancers are characterized by advanced stage and metastatic disease at presentation. They tend to be enriched with squamous and small cell/neuroendocrine features and inactivating mutations and deletions of TP53 and RB1. Basal cancers can be divided into “epithelial” and “mesenchymal” (also known as “claudin low”) subsets, and a portion of the latter form a “neuroendocrine/neuronal” subset that is associated with particularly poor survival. Luminal cancers are often enriched with papillary histopathological features and activating mutations in FGFR3, and they can also be divided into additional subsets based on differential stromal cell infiltration, relative genomic instability, and high- versus low-level expression of carcinoma in situ (CIS) gene expression signatures. Importantly, the bladder cancer molecular subtypes display differential sensitivities to neoadjuvant chemotherapy and immune checkpoint blockade, and preliminary data also suggest that they respond differently to radiation with or without hypoxia modulation. Ongoing studies are investigating the relevance of the molecular subtypes to the bladder cancer histopathological variants and to upper tract urothelial cancer.

Summary

The bladder cancer molecular subtypes were associated with different prognoses and responses to conventional and targeted therapies in retrospective studies. If validated in prospective studies, molecular subtyping will be integrated into bladder cancer clinical management.

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Authors and Affiliations

  1. Johns Hopkins Greenberg Bladder Cancer Institute and Brady Urological Institute, Johns Hopkins University, Marburg 149, 600 North Wolfe Street, Baltimore, MD, 21287, USA

    David J. McConkey & Woonyoung Choi

Authors
  1. David J. McConkey
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  2. Woonyoung Choi
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Correspondence to David J. McConkey.

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David J. McConkey and Woonyoung Choi declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genitourinary Cancers

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McConkey, D.J., Choi, W. Molecular Subtypes of Bladder Cancer. Curr Oncol Rep 20, 77 (2018). https://doi.org/10.1007/s11912-018-0727-5

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  • DOI: https://doi.org/10.1007/s11912-018-0727-5

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