Abstract
To examine the excretion of urinary epidermal growth factor (EGF) in urological diseases and the relationship of EGF urine levels with transitional cell carcinoma (TCC), we measured the concentration of EGF by radioimmunoassay. The series comprised patients with active TCC (n=50), others in tumor-free status (n=29) and with non-neoplastic inflammatory diseases (n=43), and normal controls (n=50). Urinary EGF values were lower in patients with urological diseases of different etiologies than in normal controls (P<0.005). Mean EGF levels of patients who had previous bladder tumor resection (n=21) were not statistically different from normal controls (P=0.2). For patients with active TCC, EGF urine levels showed a significant inverse relationship to increasing tumor grade (P=0.02). In addition, subjects who had received nephrectomy for pelvic carcinoma (n=8) showed significantly lower mean EGF values than those with intact kidneys (n=21), irrespective of sex (P<0.05). Immunostaining of EGF on non-neoplastic kidney (n=9) revealed reactivity in the distal convoluted tubules and thick ascending limbs of Henle. Our results suggest that the kidney is the major source of urinary EGF. Its excretion in urine is decreased in both inflammatory and neoplastic diseases of the urinary tract. EGF may play an important part in the biological activity of TCC. Further study is indicated to investigate the monitoring of EGF urine levels as a marker of recurrence for EGF receptor-positive TCC.
Similar content being viewed by others
References
Berger MS, Greenfield C, Gullick WJ, Haley J, Downward J, Neal DE, Harris AL, Waterfield MD (1987) Evaluation of epiderrnal growth factor receptors in bladder tumours. Br J Cancer 56:533
Carperter G, Cohen S (1990) Epidermal growth factor. J Biol Chem 265:7709
Chow NH, Tzai TS, Lin SN, Chan SH, Tang MJ (1993) Reappraisal of the biological role of epidermal growth factor recepter (EGFR) in transitional cell carcinoma. Eur Urol 24:140
Coutre PL, Bock S, Jakse G, Petrides PE (1992) Immunoreactive low-molecular-weight epidermal factor in urine of patients with renal cell carcinoma. Urol Res 20:293
Fuse H, Mizuno I, Sakamoto M, Kataya AT (1992) Epidermal growth factor in urine from patients with urothelial tumors. Urol Int 48:261
Hemstreet GP III, Rollins S, Jones, P, Rao JY, Hurst RE, Bonner RB, Hewett T, Smith BG (1991) Identification of a high risk subgroup of grade 1 transitional cell carcinoma using image analysis based deoxyribonucleic acid ploidy analysis of tumor tissue. J Urol 146:1525
Herr HW, Badalament RA, Amato DA, Laudone VP, Fair W, Whitmore WF (1989) Superficial bladder cancer treated with bacillus Calmette-Guérin: a multivariate analysis of factors affecting tumor progression. J Urol 141:22
Holm-Bentzen M, Lose G, Sorensen K, Jorgensen L, Nexo E (1987) Chronic cystitis: excretion of epidermal growth factor (EGF)/urogastrone (URO). Urol Res 15:203
Kiemeney LALM, Witjes JA, Verbeek ALM, Heijibroek RP, Debruyne et al. (1993) The clinical epidemiology of superficial bladder cancer. Br J Cancer 67:806
Kristensen JK, Lose G, Lund F, Nexo E (1988) Epidermal growth factor in urine from patients with urinary bladder tumors. Eur Urol 14:313
Kuranami M, Yamaguchi K, Fuchigami M, Imanishi K, Watanabe T, Abe K, Asanuma F, Hiki Y (1991) Effect of urine on clonal growth of human bladder cancer cell lines. Cancer Res 51:4631
Kvist N, Nexo E (1989) Epidermal growth factor in urine after kidney transplantation in humans. Urol Res 17:255
Lakshmanan J, Salido EC, Lam R, Fisher DA (1992) Epidermal growth factor prohormone is secreted in human urine. Am J Physiol 263:E142
Lau JLT, Fowler JE, Ghosh L (1988) Epidermal growth factor in the normal and neoplastic kidney and bladder. J Urol 139:170
Matilla AL (1986) Human urinary epidermal growth factor: effects of age, sex and female endocrine status. Life Sci 39:1879
Mattila AL, Pasternack A, Vinikka L, Perheentupa J (1986) Subnormal concentrations of urinary epidermal growth factor in patients with kidney diseases. J Clin Endocrinol Metab 67:1180
Messing EM (1990) Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma. Cancer Res 50:2530
Messing EM, Reznikoff CA (1987) Normal and malignant human urothelium: in vitro effects of epidermal growth factor. Cancer Res 47:2230
Miller SB, Rogers SA, Estes CE, Hammerman MR (1992) Increased distal nephron EGF content and altered distribution of peptide in compensatory renal hypertrophy. Am J Physiol 262:F1032
Neal DE, Marsh C, Bennett MK, Abel PD, Hall RR, Sainsbury JRC, Harris AL (1985) Epidermal growth factor receptors in human bladder cancer: comparison of invasive and superficial tumors. Lancet I:366
Neal DE, Sharples L, Smith K, Fennelly J, Hall RR, Harris AL (1990) The epidermal growth factor receptor and the prognosis of bladder cancer. Cancer 65:1619
Norming U, Tribukait B, Nyman CR, Nilsson B, Wang N (1992) Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder. J Urol 148:1420
Poulsen SS, Nexo E, Olsen PS, Hess J, Kirkegaard P (1986) Immunohistochemical localization of epidermal growth factor in rat and man. Histochemistry 85:389
Salido EC, Lakshmanan J, Fisher DA, Barajas L (1991) Immunocytochemical localization of epidermal growth factor prohormone in adult human kidney. Clin Res 39:112A
Stoll DM, King LE, McNeil L, Orth DN (1988) Human urinary epidermal growth factor excretion: age, sex and race dependence. J Clin Endocrinol Metab 67:361
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chow, N.H., Tzai, T.S., Cheng, P.E. et al. An assessment of immunoreactive epidermal growth factor in urine of patients with urological diseases. Urol. Res. 22, 221–225 (1994). https://doi.org/10.1007/BF00541896
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00541896