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
(2024) In American Journal of Surgical Pathology 48(1). p.32-42- Abstract
- 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,... (More)
- 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. © 2024 Lippincott Williams and Wilkins. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2472d761-3763-4331-a38b-0fee53323648
- author
- Warrick, J.I. ; Höglund, M. LU and Cheng, Liang
- author collaboration
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- basal, basal-squamous, bladder cancer, genomically unstable, luminal, microenvironment, molecular subtype, urothelial-like, Biomarkers, Tumor, Humans, Prognosis, Tumor Microenvironment, Urinary Bladder, Urinary Bladder Neoplasms, BCG vaccine, fibroblast growth factor receptor 3, protein, rb1 protein, unclassified drug, tumor marker, Article, basal bladder cancer, BCG vaccination, cancer recurrence, cancer staging, cancer surgery, cancer therapy, consensus development, cystectomy, diagnostic value, human, luminal bladder cancer, medical society, morphometry, neoadjuvant therapy, neuroendocrine bladder cancer, practice guideline, signal transduction, squamous bladder cancer, therapy escalation, tumor microenvironment, bladder, bladder tumor, genetics, pathology, prognosis
- in
- American Journal of Surgical Pathology
- volume
- 48
- issue
- 1
- pages
- 32 - 42
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85180286438
- pmid:37199442
- ISSN
- 0147-5185
- DOI
- 10.1097/PAS.0000000000002053
- language
- English
- LU publication?
- yes
- id
- 2472d761-3763-4331-a38b-0fee53323648
- date added to LUP
- 2025-10-16 10:57:46
- date last changed
- 2025-10-17 03:00:14
@article{2472d761-3763-4331-a38b-0fee53323648,
abstract = {{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. © 2024 Lippincott Williams and Wilkins. All rights reserved.}},
author = {{Warrick, J.I. and Höglund, M. and Cheng, Liang}},
issn = {{0147-5185}},
keywords = {{basal; basal-squamous; bladder cancer; genomically unstable; luminal; microenvironment; molecular subtype; urothelial-like; Biomarkers, Tumor; Humans; Prognosis; Tumor Microenvironment; Urinary Bladder; Urinary Bladder Neoplasms; BCG vaccine; fibroblast growth factor receptor 3; protein; rb1 protein; unclassified drug; tumor marker; Article; basal bladder cancer; BCG vaccination; cancer recurrence; cancer staging; cancer surgery; cancer therapy; consensus development; cystectomy; diagnostic value; human; luminal bladder cancer; medical society; morphometry; neoadjuvant therapy; neuroendocrine bladder cancer; practice guideline; signal transduction; squamous bladder cancer; therapy escalation; tumor microenvironment; bladder; bladder tumor; genetics; pathology; prognosis}},
language = {{eng}},
number = {{1}},
pages = {{32--42}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{American Journal of Surgical Pathology}},
title = {{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}},
url = {{http://dx.doi.org/10.1097/PAS.0000000000002053}},
doi = {{10.1097/PAS.0000000000002053}},
volume = {{48}},
year = {{2024}},
}