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The Lund Molecular Taxonomy Applied to Non-Muscle-Invasive Urothelial Carcinoma

Marzouka, Nour-Al-Dain LU ; Eriksson, Pontus LU ; Bernardo, Carina LU orcid ; Hurst, Carolyn D ; Knowles, Margaret A ; Sjödahl, Gottfrid LU ; Liedberg, Fredrik LU and Höglund, Mattias LU (2022) In Journal of Molecular Diagnostics 24(9). p.992-1008
Abstract

The precise classification of tumors into relevant molecular subtypes will facilitate both future research and optimal treatment. Here, the Lund Taxonomy system for molecular classification of urothelial carcinoma was applied to two large and independent cohorts of non-muscle-invasive tumors. Of 752 tumors classified, close to 100% were of the luminal subtypes, 95% urothelial-like (Uro; UroA, UroB, or UroC) and 5% genomically unstable. The obtained subtype structure organized the tumors into groups with specific and coherent gene mutation, genomic, and clinical profiles. The intrasubtype variability in the largest group of tumors, UroA, was caused by infiltration and proliferation, not considered as cancer cell type-defining properties.... (More)

The precise classification of tumors into relevant molecular subtypes will facilitate both future research and optimal treatment. Here, the Lund Taxonomy system for molecular classification of urothelial carcinoma was applied to two large and independent cohorts of non-muscle-invasive tumors. Of 752 tumors classified, close to 100% were of the luminal subtypes, 95% urothelial-like (Uro; UroA, UroB, or UroC) and 5% genomically unstable. The obtained subtype structure organized the tumors into groups with specific and coherent gene mutation, genomic, and clinical profiles. The intrasubtype variability in the largest group of tumors, UroA, was caused by infiltration and proliferation, not considered as cancer cell type-defining properties. Within the UroA subtype, a HOXB/late cell-cycle gene expression polarity was found, strongly associated with FGFR3, STAG2, and TP53 mutations, as well as with chromosome 9 losses. Kaplan-Meier analyses identified the genomically unstable subtype as a progression high-risk group, also valid in the subgroup of T1 tumors. Almost all progression events occurred within 12 months in this subtype. Also, a general progression gene signature was derived that identifies high- and low-risk tumors. All findings were demonstrated in two independent cohorts. The Lund Taxonomy system is applicable to both non-muscle- and muscle-invasive tumors and may be a useful biological framework for translational studies.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Tumor/metabolism, Carcinoma, Transitional Cell/genetics, Humans, Immunohistochemistry, Urinary Bladder Neoplasms/genetics, Urothelium/chemistry
in
Journal of Molecular Diagnostics
volume
24
issue
9
pages
992 - 1008
publisher
Elsevier
external identifiers
  • scopus:85137718093
  • pmid:35853574
ISSN
1525-1578
DOI
10.1016/j.jmoldx.2022.05.006
language
English
LU publication?
yes
additional info
Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
id
72b6cd36-265f-4359-8707-4bbb55d1a6e4
date added to LUP
2022-10-26 21:22:18
date last changed
2024-05-03 16:02:38
@article{72b6cd36-265f-4359-8707-4bbb55d1a6e4,
  abstract     = {{<p>The precise classification of tumors into relevant molecular subtypes will facilitate both future research and optimal treatment. Here, the Lund Taxonomy system for molecular classification of urothelial carcinoma was applied to two large and independent cohorts of non-muscle-invasive tumors. Of 752 tumors classified, close to 100% were of the luminal subtypes, 95% urothelial-like (Uro; UroA, UroB, or UroC) and 5% genomically unstable. The obtained subtype structure organized the tumors into groups with specific and coherent gene mutation, genomic, and clinical profiles. The intrasubtype variability in the largest group of tumors, UroA, was caused by infiltration and proliferation, not considered as cancer cell type-defining properties. Within the UroA subtype, a HOXB/late cell-cycle gene expression polarity was found, strongly associated with FGFR3, STAG2, and TP53 mutations, as well as with chromosome 9 losses. Kaplan-Meier analyses identified the genomically unstable subtype as a progression high-risk group, also valid in the subgroup of T1 tumors. Almost all progression events occurred within 12 months in this subtype. Also, a general progression gene signature was derived that identifies high- and low-risk tumors. All findings were demonstrated in two independent cohorts. The Lund Taxonomy system is applicable to both non-muscle- and muscle-invasive tumors and may be a useful biological framework for translational studies.</p>}},
  author       = {{Marzouka, Nour-Al-Dain and Eriksson, Pontus and Bernardo, Carina and Hurst, Carolyn D and Knowles, Margaret A and Sjödahl, Gottfrid and Liedberg, Fredrik and Höglund, Mattias}},
  issn         = {{1525-1578}},
  keywords     = {{Biomarkers, Tumor/metabolism; Carcinoma, Transitional Cell/genetics; Humans; Immunohistochemistry; Urinary Bladder Neoplasms/genetics; Urothelium/chemistry}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{992--1008}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular Diagnostics}},
  title        = {{The Lund Molecular Taxonomy Applied to Non-Muscle-Invasive Urothelial Carcinoma}},
  url          = {{http://dx.doi.org/10.1016/j.jmoldx.2022.05.006}},
  doi          = {{10.1016/j.jmoldx.2022.05.006}},
  volume       = {{24}},
  year         = {{2022}},
}