To evaluate the mRNA expression of lymphangiogenesis and proliferation markers and to examine its association with histopathological characteristics and clinical outcome in patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC).
Gene expression analysis of the vascular endothelial growth -C and -D (VEGF-C/-D), its receptor VEGF receptor-3 (VEGFR-3), MKI67, and RACGAP1 was performed in 108 patients after radical cystectomy and their correlation with clinical-pathological parameters was investigated. Uni- and multivariate regression analyses were used to identify predictors for cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS) after RC.
The expression of RACGAP1 and VEGFR-3 showed an association with a higher pT stage (P = 0.049; P = 0.009). MKI67 showed an association with a high-grade urothelial carcinoma of the bladder (P = 0.021). VEGFR-3 expression was significantly associated with the presence of lymphovascular invasion (LVI) (P = 0.016) and lymph node metastases (pN+) (P = 0.028). With the univariate analysis, overexpression of VEGFR-3 (P = 0.029) and the clinical-pathological parameters pT stage (P < 0.0001), pN+ (P = 0.0004), LVI (P < 0.0001) and female gender (P = 0.021) were significantly associated with a reduced CSS. Multivariate analysis identified a higher pT stage (P = 0.017) and LVI (P = 0.008) as independent predictors for reduced CSS. Independent predictors for reduced OS were a higher pT stage (P = 0.0007) and LVI (P = 0.0021), while overexpression of VEGF-D was associated with better OS (P < 0.0001).
The mRNA expression of the investigated markers showed associations with common histopathological parameters. Increased expression of VEGF-D is independently associated with better overall survival.
Urologic oncology. 2018 Nov 13 [Epub ahead of print]
Thomas Martini, Jakob Heinkele, Roman Mayr, Cleo-Aron Weis, Felix Wezel, Sarah Wahby, Markus Eckstein, Thomas Schnöller, Johannes Breyer, Ralph Wirtz, Manuel Ritter, Christian Bolenz, Philipp Erben
Department of Urology, University of Ulm, Ulm, Germany. Electronic address: ., Department of Urology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Germany., Institute of Pathology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Department of Urology, University of Ulm, Ulm, Germany., Institute of Pathology, University of Erlangen-Nüremberg, Erlangen, Germany., STRATIFYER Molecular Pathology GmbH, Cologne, Germany; Institute of Pathology, The St. Elisabeth Hospital Köln-Hohenlind, Cologne, Germany., Department of Urology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: .