Immunoreactive low-molecular-weight epidermal growth factor in urine of patients with renal cell carcinoma

A specific heterogeneous enzyme-linked immunosorbent assay (ELISA) has been established in order to determine levels of low-molecular-weight epidermal growth factor (EGF) in the urine of patients with renal cell carcinoma who had undergone unilateral radical nephrectomy. Urine specimens, i.e., 20 pre- and postsurgical specimens from a group of patients and 22 from a control group, were assayed after the urine had been freed from high-molecular-weight proteins (greater than 30 kDa) and salts. EGF levels were expressed as urinary EGF/creatinine ratios, and a highly significant decrease (alpha = 0.0005 by Student's t-test) of urinary EGF was found in the patient group prior to surgery. The cancer patients also showed an additional loss of urinary EGF after unilateral nephrectomy (alpha = 0.0005 by Student's t-test). These data correlate with our previous findings that pro-EGF gene expression is decreased in human renal carcinoma and support the concept that low-molecular-weight urinary EGF is derived from high-molecular-weight kidney pro-EGF.