DIFFERENT ANGIOGENIC PATHWAYS CHARACTERIZE SUPERFICIAL AND INVASIVE BLADDER-CANCER

We have investigated by RNase protection analysis the expression of 2 angiogenic factors in 45 primary bladder tumors and 8 normal bladders. Expression of vascular endothelial growth factor (VEGF) was 3-fold hi gher and that of platelet-derived endothelial cell growth factor was 4 0-fold higher in tumors compared to normal bladder. How ever, the fact ors were differentially expressed in different stages of the cancer. E xpression of VEGF in superficial tumors was 4-fold higher than in inva sive tumors and 10-fold higher than in normal bladder (superficial ver sus invasive, P < 0.0006; superficial versus normal, P < 0.0002). Expr ession of platelet-derived endothelial cell growth factor in invasive tumors was 33-fold higher than in superficial tumors and 260-fold high er than in normal bladder (invasive versus superficial, P < 0.0001; in vasive versus normal, P < 0.0003). In well differentiated or moderatel y differentiated superficial tumors which had invaded the lamina propr ia (pT1G1/2) VEGF expression was 4-fold higher in tumors which subsequ ently recurred at 3 months compared to those which did not recur (P < 0.002). Thus there are two distinct angiogenic pathways involved in di fferent stages of bladder cancer, which is in keeping with the evidenc e for two different genetic pathways. Elevated VEGF expression predict s early recurrence of pT1G1/2 tumors.