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Toward a Molecular Pathologic Classification of Urothelial Carcinoma.

Sjödahl, Gottfrid LU ; Lövgren, Kristina LU ; Lauss, Martin LU ; Hultman Patschan, Oliver LU ; Gudjonsson, Sigurdur LU ; Chebil, Gunilla; Aine, Mattias LU ; Eriksson, Pontus LU ; Månsson, Wiking LU and Lindgren, David LU , et al. (2013) In American Journal of Pathology 183(3). p.681-691
Abstract
We recently defined molecular subtypes of urothelial carcinomas according to whole genome gene expression. Herein we describe molecular pathologic characterization of the subtypes using 20 genes and IHC of 237 tumors. In addition to differences in expression levels, the subtypes show important differences in stratification of protein expression. The selected genes included biological features central to bladder cancer biology, eg, cell cycle activity, cellular architecture, cell-cell interactions, and key receptor tyrosine kinases. We show that the urobasal (Uro) A subtype shares features with normal urothelium such as keratin 5 (KRT5), P-cadherin (P-Cad), and epidermal growth factor receptor (EGFR) expression confined to basal cells, and... (More)
We recently defined molecular subtypes of urothelial carcinomas according to whole genome gene expression. Herein we describe molecular pathologic characterization of the subtypes using 20 genes and IHC of 237 tumors. In addition to differences in expression levels, the subtypes show important differences in stratification of protein expression. The selected genes included biological features central to bladder cancer biology, eg, cell cycle activity, cellular architecture, cell-cell interactions, and key receptor tyrosine kinases. We show that the urobasal (Uro) A subtype shares features with normal urothelium such as keratin 5 (KRT5), P-cadherin (P-Cad), and epidermal growth factor receptor (EGFR) expression confined to basal cells, and cell cycle activity (CCNB1) restricted to the tumor-stroma interface. In contrast, the squamous cell cancer-like (SCCL) subtype uniformly expresses KRT5, P-Cad, EGFR, KRT14, and cell cycle genes throughout the tumor parenchyma. The genomically unstable subtype shows proliferation throughout the tumor parenchyma and high ERBB2 and E-Cad expression but absence of KRT5, P-Cad, and EGFR expression. UroB tumors demonstrate features shared by both UroA and SCCL subtypes. A major transition in tumor progression seems to be loss of dependency of stromal interaction for proliferation. We present a simple IHC/histology-based classifier that is easy to implement as a standard pathologic evaluation to differentiate the three major subtypes: urobasal, genomically unstable, and SCCL. These three major subtypes exhibit important prognostic differences. (Less)
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American Journal of Pathology
volume
183
issue
3
pages
681 - 691
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000323866000006
  • pmid:23827819
  • scopus:84883162217
ISSN
1525-2191
DOI
10.1016/j.ajpath.2013.05.013
language
English
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yes
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f554a054-e126-49e5-9c68-116c49d71f21 (old id 3956158)
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http://www.ncbi.nlm.nih.gov/pubmed/23827819?dopt=Abstract
date added to LUP
2013-08-02 10:56:41
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2019-08-07 01:33:47
@article{f554a054-e126-49e5-9c68-116c49d71f21,
  abstract     = {We recently defined molecular subtypes of urothelial carcinomas according to whole genome gene expression. Herein we describe molecular pathologic characterization of the subtypes using 20 genes and IHC of 237 tumors. In addition to differences in expression levels, the subtypes show important differences in stratification of protein expression. The selected genes included biological features central to bladder cancer biology, eg, cell cycle activity, cellular architecture, cell-cell interactions, and key receptor tyrosine kinases. We show that the urobasal (Uro) A subtype shares features with normal urothelium such as keratin 5 (KRT5), P-cadherin (P-Cad), and epidermal growth factor receptor (EGFR) expression confined to basal cells, and cell cycle activity (CCNB1) restricted to the tumor-stroma interface. In contrast, the squamous cell cancer-like (SCCL) subtype uniformly expresses KRT5, P-Cad, EGFR, KRT14, and cell cycle genes throughout the tumor parenchyma. The genomically unstable subtype shows proliferation throughout the tumor parenchyma and high ERBB2 and E-Cad expression but absence of KRT5, P-Cad, and EGFR expression. UroB tumors demonstrate features shared by both UroA and SCCL subtypes. A major transition in tumor progression seems to be loss of dependency of stromal interaction for proliferation. We present a simple IHC/histology-based classifier that is easy to implement as a standard pathologic evaluation to differentiate the three major subtypes: urobasal, genomically unstable, and SCCL. These three major subtypes exhibit important prognostic differences.},
  author       = {Sjödahl, Gottfrid and Lövgren, Kristina and Lauss, Martin and Hultman Patschan, Oliver and Gudjonsson, Sigurdur and Chebil, Gunilla and Aine, Mattias and Eriksson, Pontus and Månsson, Wiking and Lindgren, David and Fernö, Mårten and Liedberg, Fredrik and Höglund, Mattias},
  issn         = {1525-2191},
  language     = {eng},
  number       = {3},
  pages        = {681--691},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Toward a Molecular Pathologic Classification of Urothelial Carcinoma.},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2013.05.013},
  volume       = {183},
  year         = {2013},
}