Maximilian Christian Kriegmair1, Matthias Balk2, Ralph Wirtz3, Annette Steidler2, Cleo-Aron Weis4, Johannes Breyer5, Arndt Hartmann6, Christian Bolenz7, Philipp Erben2. 1. Department of Urology, University Medical Centre Mannheim, Mannheim, Germany maximilian.kriegmair@medma.uni-heidelberg.de. 2. Department of Urology, University Medical Centre Mannheim, Mannheim, Germany. 3. Stratifyer Molecular Pathology, Köln, Germany. 4. Institute of Pathology, University Medical Centre Mannheim, Mannheim, Germany. 5. Department of Urology, University of Regensburg, Regensburg, Germany. 6. Institute of Pathology, University Erlangen-Nuernberg, Erlangen, Germany. 7. Department of Urology, University of Ulm, Ulm, Germany.
Abstract
AIM: To evaluate the prognostic role of the p53-upstream inhibitors MDM2, MDM4 and its splice variant MDM4-S in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: mRNA Expression levels of MDM2, MDM4 and MDM4-S were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) in 75 RC samples. Logistic regression analyses identified predictors of recurrence-free (RFS) and cancer-specific survival (CSS). RESULTS: High expression was found in 42% (MDM2), 27% (MDMD4) and 91% (MDM4-S) of tumor specimens. Increased MDM2 expression was significantly associated with higher tumor stage (p=0.05) and lymphovascular invasion (LVI) (p=0.041). In the univariate analysis, low MDM4 expression (hazard ratio (HR)=5.93; p=0.002; HR=3.00; p=0.047), but not MDM2 (HR=1.63; p=0.222; HR=1.59; p=0.27), were associated with RFS and CSS. In the multivariate analysis, the combination of low MDM4 and high MDM2 was significant for RFS and CSS (HR=14.9; p=0.001; HR=5.63; p=0.019). CONCLUSION: The combination of MDM2 and MDM4 expression is an independent predictor in patients undergoing RC for MIBC. Copyright
AIM: To evaluate the prognostic role of the p53-upstream inhibitors MDM2, MDM4 and its splice variant MDM4-S in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: mRNA Expression levels of MDM2, MDM4 and MDM4-S were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) in 75 RC samples. Logistic regression analyses identified predictors of recurrence-free (RFS) and cancer-specific survival (CSS). RESULTS: High expression was found in 42% (MDM2), 27% (MDMD4) and 91% (MDM4-S) of tumor specimens. Increased MDM2 expression was significantly associated with higher tumor stage (p=0.05) and lymphovascular invasion (LVI) (p=0.041). In the univariate analysis, low MDM4 expression (hazard ratio (HR)=5.93; p=0.002; HR=3.00; p=0.047), but not MDM2 (HR=1.63; p=0.222; HR=1.59; p=0.27), were associated with RFS and CSS. In the multivariate analysis, the combination of low MDM4 and high MDM2 was significant for RFS and CSS (HR=14.9; p=0.001; HR=5.63; p=0.019). CONCLUSION: The combination of MDM2 and MDM4 expression is an independent predictor in patients undergoing RC for MIBC. Copyright
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