mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20⁺/KRT5-, 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20⁺/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).

International journal of molecular sciences. 2018 Oct 30*** epublish ***

Markus Eckstein, Ralph Markus Wirtz, Matthias Gross-Weege, Johannes Breyer, Wolfgang Otto, Robert Stoehr, Danijel Sikic, Bastian Keck, Sebastian Eidt, Maximilian Burger, Christian Bolenz, Katja Nitschke, Stefan Proubsky, Arndt Hartmann, Philipp Erben

Institute of Pathology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. ., STRATIFYER Molecular Pathology GmbH, 50935 Cologne, Germany. ., Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany. ., Department of Urology, University of Regensburg, 93053 Regensburg, Germany. ., Department of Urology, University of Regensburg, 93053 Regensburg, Germany. ., Institute of Pathology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. ., Department of Urology and Pediatric Urology, University Hospital Erlangen, 91058 Erlangen, Germany. ., Department of Urology and Pediatric Urology, University Hospital Erlangen, 91058 Erlangen, Germany. ., Institute of Pathology at the St Elisabeth Hospital Köln-Hohenlind, 50935 Cologne, Germany. ., Department of Urology, University of Regensburg, 93053 Regensburg, Germany. ., Department of Urology, University of Ulm, 89081 Ulm, Germany. ., Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany. ., Department of Pathology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany. ., Institute of Pathology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. ., Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany. .

E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe