Prognostic significance of angiogenesis and immunoreactivity of cathepsin D and type IV collagen in high-grade stage T1 primary bladder cancer

Objectives, To assess the prognostic significance of biologic parameters su ch as angiogenesis, expression of cathepsin D (a lysosomal protease), and d egradation of type IV collagen (a basement membrane protein), we studied 20 patients with primary grade III Stage T1 transitional cell carcinoma of th e bladder. Methods. Endothelial cells were labeled immunohistochemically using factor VIII-related antigen. The vascular surface density (VSD) and the microvesse l number (NVES) were assessed by means of stereology. The tumor tissues wer e also analyzed by immunohistochemical methods for the expression of cathep sin D and the staining pattern of type IV collagen. Results. Eight patients (40%) having either recurrence or progressive disea se showed greater NVES and VSD values (P = 0.002 and P = 0.01, respectively ) than patients without. The significance of vascular parameters was found to be statistically independent from coexisting carcinoma in situ, bacille Calmette-Guerin [BCG) treatment, tumor size, and number. Additionally, thes e parameters did not show statistical significance between progressive and recurrent tumors. However, tumors with solid morphologic features had highe r VSD values and a significantly greater rate of recurrence or progression (P = 0.01 and P = 0.07, respectively). Tissue from 17 (85%) of 20 tumors sh owed absent or patchy basement membrane staining for type IV collagen, and 12 (60%) showed strong immunoreactivity for cathepsin D antibody. There wer e no differences for either molecule with either BCG treatment or other par ameters related to prognosis, Conclusions. Angiogenesis may have an independent role in predicting progno sis in grade III Stage TI bladder carcinoma. Grade III Stage pT1 tumors wit h solid morphologic features have higher angiogenetic activity and a worse prognosis. Cathepsin D and type IV collagen do not seem to play a role in p redicting biologic behavior. UROLOGY 54: 50-55, 1999. (C) 1999, Elsevier Sc ience Inc.