International Society of Urological Pathology Consensus Conference on Current Issues in Bladder Cancer. Working Group 4: Molecular Subtypes of Bladder Cancer - Principles of Classification and Emerging Clinical Utility

Joshua I. Warrick, Hikmat Al-Ahmadie, David M. Berman, Peter C. Black, Thomas W. Flaig, Mattias Höglund, Lukas Bubendorf, Theodorus H. Van Der Kwast, Liang Cheng, Adebowale Adeniran, Hikmat Al-Ahimadie, Fernando Algaba, Yves Allory, Selina Bhattarai, Peter Black, David Berman, Simone Bertz, Lukas Bubendorf, Birgitte Carlsen, Rita CarvalhoLiang Cheng, Obinna Chijioke, Yong Mee Cho, Eva Comperat, Isabela Di Cunha, Julien Dagher, Isabella De Cunha, Brett Delahunt, Michelle Downes, Thomas Flaig, Achim Fleischmann, Cosmin Florescu, Jacqueline Fontugne, Vera Genitsch, Guro Horni Gløersen, Michael Von Gunten, Rainer Grobholz, Donna Hanselarndt Hartmann, Loren Herrera Hernandez, Mattias Hogland, Jiaoti Huang, Brad Jensen, Kenneth Iczkowski, Rafael Jimenez, Bojana Jovanovic, Ashish Kamat, Jens Koellermann, Trevor Levin, Fredrik Liedberg, Antonio Lopez-Beltran, Anand C. Loya, Marianne Lyngra, Teresa McHale, Khadidja Mokeddem, George Netto, Maya Nourieh, Declan O'Rourke, Irina Alexandra Ostahi, Gladell Paner, Maria M. Picken, Flavia Guzman Pineda, Camelia Radulescu Maria Raspollini, Henning Reis, Shi Ruoyu, Hemamali Samaratunga, Remi Semba, Nigam Shah, Steven Shen, Steven Smith, Tovia Smith, John Srigley, Sueli Suzigan, Nicole Swarbrick, Ildiko Szalay, Inger Talleraas, Jean Christophe Tille, Marieta Toma, Isabel Trias, Toyonori Tsuzuki, Theodorus Van Der Kwast, Bas Van Rhijn, Murali Varma, Sofie Verbeke, Sangeeta Verma, Tatjana Vlajnic, Ljiljana Vlatkovic, Anne Warren, Joshua Warrick, Sean Williamson, Sara Wobker, Clifton Woods, Chen Yang, Ghilsuk Yoon

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4 Scopus citations


Molecular subtyping has been a major focus of bladder cancer research over the past decade. Despite many promising associations with clinical outcomes and treatment response, its clinical impact has yet to be defined. As part of the 2022 International Society of Urological Pathology Conference on Bladder Cancer, we reviewed the current state of the science for bladder cancer molecular subtyping. Our review included several different subtyping systems. We derived the following 7 principles, which summarize progress and challenges of molecular subtyping: (1) bladder cancer has 3 major molecular subtypes: luminal, basal-squamous, and neuroendocrine; (2) signatures of the tumor microenvironment differ greatly among bladder cancers, particularly among luminal tumors; (3) luminal bladder cancers are biologically diverse, and much of this diversity results from differences in features unrelated to the tumor microenvironment, such as FGFR3 signaling and RB1 inactivation; (4) molecular subtype of bladder cancer associates with tumor stage and histomorphology; (5) many subtyping systems include idiosyncrasies, such as subtypes recognized by no other system; (6) there are broad fuzzy borders between molecular subtypes, and cases that fall on these fuzzy borders are often classified differently by different subtyping systems; and (7) when there are histomorphologically distinct regions within a single tumor, the molecular subtypes of these regions are often discordant. We reviewed several use cases for molecular subtyping, highlighting their promise as clinical biomarkers. Finally, we conclude that data are currently insufficient to support the routine use of molecular subtyping to guide bladder cancer management, an opinion shared with the majority of conference attendees. We also conclude that molecular subtype should not be considered an "intrinsic" property of a tumor but should instead be considered the result of a specific laboratory test, performed using a specific testing platform and classification algorithm, validated for a specific clinical application.

Original languageEnglish (US)
Pages (from-to)E32-E42
JournalAmerican Journal of Surgical Pathology
Issue number1
StatePublished - Jan 1 2024

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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