Toward a Molecular Pathologic Classification of Urothelial Carcinoma.

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.

• Författare: Gottfrid Sjödahl; Kristina Lövgren; Martin Lauss; Oliver Hultman Patschan; Sigurdur Gudjonsson; Gunilla Chebil; Mattias Aine; Pontus Eriksson; Wiking Månsson; David Lindgren; Mårten Fernö; Fredrik Liedberg; Mattias Höglund
• 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: http://www.ncbi.nlm.nih.gov/pubmed/23827819?dopt=Abstract; http://dx.doi.org/10.1016/j.ajpath.2013.05.013
• 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