Toward a Molecular Pathologic Classification of Urothelial Carcinoma.
Författare
Summary, in English
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.
Avdelning/ar
- Urological research, Malmö
- Bröstcancer-genetik
- Urologi
- Genomiska analyser av urinblåscancer
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2013
Språk
Engelska
Sidor
681-691
Publikation/Tidskrift/Serie
American Journal of Pathology
Volym
183
Issue
3
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Investigative Pathology
Ämne
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Urological research, Malmö
- Urology
- Urothelial Cancer Genomics
ISBN/ISSN/Övrigt
- ISSN: 1525-2191