Cancer Management and Research (Aug 2021)

The Prognostic Value of FGFR3 Expression in Patients with T1 Non-Muscle Invasive Bladder Cancer

  • Sikic D,
  • Taubert H,
  • Breyer J,
  • Eckstein M,
  • Weyerer V,
  • Keck B,
  • Kubon J,
  • Otto W,
  • Worst TS,
  • Kriegmair MC,
  • Erben P,
  • Hartmann A,
  • Wullich B,
  • Wirtz RM,
  • Wach S

Journal volume & issue
Vol. Volume 13
pp. 6567 – 6578

Abstract

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Danijel Sikic,1,2 Helge Taubert,1,2 Johannes Breyer,3 Markus Eckstein,2,4 Veronika Weyerer,2,4 Bastian Keck,1,2 Jennifer Kubon,1,2 Wolfgang Otto,3 Thomas S Worst,5 Maximilian C Kriegmair,5 Philipp Erben,5 Arndt Hartmann,2,4 Bernd Wullich,1,2 Ralph M Wirtz,6 Sven Wach1,2 1Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; 2Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany; 3Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Regensburg, Germany; 4Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; 5Department of Urology and Urosurgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 6STRATIFYER Molecular Pathology GmbH, Cologne, GermanyCorrespondence: Danijel SikicDepartment of Urology and Pediatric Urology, University Hospital Erlangen, Universitätsstraße 12, Erlangen, 91054, GermanyTel +49 9131 822 3178Fax +49 9131 822 3179Email [email protected]: Fibroblast growth factor receptor 3 (FGFR3) alterations are frequent in non-muscle-invasive bladder cancer (NMIBC), although current data regarding the prognostic and therapeutic relevance are inconsistent. We analyzed the prognostic role of FGFR3 mRNA expression in stage T1 NMIBC.Patients and Methods: The mRNA expression of FGFR3 and cyclin-dependent kinase inhibitor 2A (CDKN2A) was measured by RT-qPCR in 80 patients with stage T1 NMIBC treated with transurethral resection of the bladder and correlated with clinical data and KRT5 and KRT20 expression, used as surrogate markers for basal and luminal subtypes, respectively.Results: FGFR3 and CDKN2A transcript levels were not correlated. FGFR3 expression was associated with the expression of KRT5 (p=0.002) and KRT20 (p < 0.001). CDKN2A expression was negatively correlated with KRT5 (p=0.030). In Kaplan–Meier analysis and univariable Cox regression analysis, high FGFR3 expression was associated with significantly reduced recurrence-free survival (RFS) (HR=3.78; p < 0.001) and improved overall survival (OS) (HR=0.50; p=0.043), while high CDKN2A expression was associated with reduced OS (HR=2.34; p=0.034). Patient age was the only clinicopathological parameter associated with reduced OS (HR=2.29; p=0.022). No parameter was an independent prognostic factor in multivariable analysis. Next, we stratified the patients depending on their lineage differentiation. In univariable analysis, the prognostic effect of FGFR3 and CDKN2A was observed primarily in patients demonstrating high expression of KRT5 or KRT20, whereas high FGFR3 expression was associated with significantly reduced RFS, irrespective of instillation therapy.Conclusion: Stage T1 NMIBC patients with high FGFR3 expression show shorter RFS but better OS than patients with low FGFR3 expression.Keywords: biomarker, CDKN2A, FGFR3, NMIBC, prognosis

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