EPIDERMAL GROWTH FACTOR-RESPONSIVE AND EPIDERMAL GROWTH FACTOR-REFRACTORY CARCINOMAS INITIATED WITH N-METHYL-N-NITROSOUREA IN RAT URINARY-BLADDER

We tested the role of epidermal growth factor (EGF) in the development of low-grade superficial bladder tumors by using a heterotopically tr ansplanted rat urinary bladder system, Weekly EGF administration (250 ng/0.5 ml of phosphate-buffered 2.1% NaCl solution) for 28 weeks into heterotopically transplanted rat urinary bladders initiated with a low dose of N-methyl-N-nitrosourea resulted in a significant increase in the incidence (17 of 25 versus 6 of 30 rats; P < 0.001) and the mean n umber of tumors per bladder (1.08 versus 0.20; P < 0.001) as compared with those for a vehicle-only group, Changing to vehicle without EGF f or the last 8 weeks resulted in tumors in 8 of 24 rats (P = 0.02 versu s the EGF group), comparable to the rate for controls, Switching from vehicle to EGF for the last 8 weeks resulted in tumors in 15 of 24 rat s, comparable to the rate in the 28-week EGF group, When tumors were d ivided into two groups according to size (>4.2 mm(3) and less than or equal to 4.2 mm(3)), expression of EGF receptor (EGF-R) was found in 2 4 of 25 ''large'' tumors as compared with 5 of 17 ''small'' tumors (P < 0.0001), The results of in situ hybridization for EGF-R correlated w ell with those of immunohistochemical study. These data suggest the po ssibility that recurrences of low-grade superficial bladder tumors are related to the continuing presence of EGF in the urine, and that bloc king of EGF-R should be evaluated as a tumor inhibitor.