The aggressiveness of urothelial carcinoma depends to a large extent on lymphovascular invasion - the prognostic contribution of related molecular markers

Aims: Bladder cancer is the second most common malignancy of the urogenital region. The majority of bladder cancer deaths occur as a consequence of metastatic disease. Blood vessel density (BVD), a surrogate marker for angiogenesis, has been shown to be predictive of progression and poor prognosis, as well as lymphatic vessel density (LVD). The aim of this study was to evaluate, in human urothelial bladder cancer (UBC), the clinical and prognostic significance of angiogenesis, lymphangiogenesis and lymphovascular invasion, assessed with the use of specific immunohistochemical markers. Methods and results: Immunohistochemistry for CD31 (a blood vessel endothelial cell marker), D2-40 (a lymphatic vessel endothelial cell marker), vascular endothelial growth factor (VEGF)-C and VEGF-receptor 3 antibodies was performed in 83 patients with urothelial carcinoma who underwent radical cystectomy. The classic histopathological characteristics, associated with lymphovascular invasion and loco-regional dissemination, had a negative influence on 5-year overall survival (OS) rates. BVD and LVD were correlated with advanced and poorly differentiated UBC with lymphovascular invasion. Blood vessel invasion (BVI) by malignant emboli assessed by CD31 staining, and lymphatic vessel invasion (LVI) by isolated malignant cells assessed by D2-40 staining significantly affected OS. VEGF-C overexpression was correlated with both BVI and LVI by single malignant cells assessed by CD31 and D2-40, respectively. BVI by malignant emboli assessed by CD31 staining remained as an independent prognostic factor. Conclusions: Patients with UBC with embolic BVI assessed by CD31 and LVI by isolated malignant cells assessed by D2-40 have a worse prognosis and may benefit from adjuvant therapies.