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Article

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

1
Institute of Pathology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
2
STRATIFYER Molecular Pathology GmbH, 50935 Cologne, Germany
3
Institute of Pathology at the St Elisabeth Hospital Köln-Hohenlind, 50935 Cologne, Germany
4
Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
5
Department of Urology, University of Regensburg, 93053 Regensburg, Germany
6
Department of Urology and Pediatric Urology, University Hospital Erlangen, 91058 Erlangen, Germany
7
Department of Urology, University of Ulm, 89081 Ulm, Germany
8
Department of Pathology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
*
Author to whom correspondence should be addressed.
On behalf of the BRIDGE Consortium.
Int. J. Mol. Sci. 2018, 19(11), 3396; https://doi.org/10.3390/ijms19113396
Received: 22 September 2018 / Revised: 14 October 2018 / Accepted: 22 October 2018 / Published: 30 October 2018
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). View Full-Text
Keywords: Bladder cancer; muscle-invasive bladder cancer; molecular diagnostics; molecular subtyping; KRT5; KRT20 Bladder cancer; muscle-invasive bladder cancer; molecular diagnostics; molecular subtyping; KRT5; KRT20
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MDPI and ACS Style

Eckstein, M.; Wirtz, R.M.; Gross-Weege, M.; Breyer, J.; Otto, W.; Stoehr, R.; Sikic, D.; Keck, B.; Eidt, S.; Burger, M.; Bolenz, C.; Nitschke, K.; Porubsky, S.; Hartmann, A.; Erben, P. mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants. Int. J. Mol. Sci. 2018, 19, 3396. https://doi.org/10.3390/ijms19113396

AMA Style

Eckstein M, Wirtz RM, Gross-Weege M, Breyer J, Otto W, Stoehr R, Sikic D, Keck B, Eidt S, Burger M, Bolenz C, Nitschke K, Porubsky S, Hartmann A, Erben P. mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants. International Journal of Molecular Sciences. 2018; 19(11):3396. https://doi.org/10.3390/ijms19113396

Chicago/Turabian Style

Eckstein, Markus; Wirtz, Ralph M.; Gross-Weege, Matthias; Breyer, Johannes; Otto, Wolfgang; Stoehr, Robert; Sikic, Danijel; Keck, Bastian; Eidt, Sebastian; Burger, Maximilian; Bolenz, Christian; Nitschke, Katja; Porubsky, Stefan; Hartmann, Arndt; Erben, Philipp. 2018. "mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants" Int. J. Mol. Sci. 19, no. 11: 3396. https://doi.org/10.3390/ijms19113396

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