Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jun;69(6):1120–1125. doi: 10.1038/bjc.1994.220

Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis.

P Lipponen 1, M Eskelinen 1
PMCID: PMC1969432  PMID: 7911031

Abstract

The expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in 234 cases of transitional cell bladder cancer. EGFR was overexpressed in 35% of cases and distinct nuclear localisation of EGFR positivity was found in 31% of the tumours. Overexpression was related to invasive growth, grade 2-3 histology, non-papillary type, DNA aneuploidy and high proliferation rate of cancer cells. The expressions of p53 and EGFR were interrelated, while expression of c-erbB-2 was independent of EGFR expression. Progression of superficial tumours, recurrence-free survival and survival were independently related to overexpression of EGFR in multivariate analysis. T category, S-phase fraction and non-papillary type included all the available prognostic information when the entire cohort was analysed by multivariate methods. The results show that overexpression of EGFR is related to several malignant features and prognosis in superficial bladder cancer. Moreover, the results suggest that overexpression of EGFR is usually a late event in bladder cancer development related to genetic instability rather than an early event in malignant transformation. Further studies are still needed to establish whether the direct measurement of cell proliferation or analysis of growth factor receptors and other oncoproteins gives more accurate prognostic information in bladder cancer.

Full text

PDF
1120

Images in this article

1122Figure 1
on p.1122

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson E. D., Rees A. R. Epidermal growth factor receptors. Mol Cell Biochem. 1981 Feb 11;34(3):129–152. doi: 10.1007/BF02359619. [DOI] [PubMed] [Google Scholar]
  2. Argilés A., Kraft N., Ootaka T., Hutchinson P., Atkins R. C. Epidermal growth factor and transforming growth factor alpha stimulate or inhibit proliferation of a human renal adenocarcinoma cell line depending on cell status: differentiation of the two pathways by G protein involvement. Cancer Res. 1992 Aug 15;52(16):4356–4360. [PubMed] [Google Scholar]
  3. Asamoto M., Hasegawa R., Masuko T., Hashimoto Y., Ueda K., Ohtaguro K., Sasaki S., Washida H., Fukushima S. Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas. Acta Pathol Jpn. 1990 May;40(5):322–326. doi: 10.1111/j.1440-1827.1990.tb01568.x. [DOI] [PubMed] [Google Scholar]
  4. Cohen S. The epidermal growth factor (EGF). Cancer. 1983 May 15;51(10):1787–1791. doi: 10.1002/1097-0142(19830515)51:10<1787::aid-cncr2820511004>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  5. Coombs L. M., Pigott D. A., Eydmann M. E., Proctor A. J., Knowles M. A. Reduced expression of TGF beta is associated with advanced disease in transitional cell carcinoma. Br J Cancer. 1993 Mar;67(3):578–584. doi: 10.1038/bjc.1993.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coombs L. M., Pigott D. A., Sweeney E., Proctor A. J., Eydmann M. E., Parkinson C., Knowles M. A. Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. Br J Cancer. 1991 Apr;63(4):601–608. doi: 10.1038/bjc.1991.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davidoff A. M., Iglehart J. D., Marks J. R. Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3439–3442. doi: 10.1073/pnas.89.8.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Engebraaten O., Bjerkvig R., Pedersen P. H., Laerum O. D. Effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferative, migratory and invasive capacities of human brain-tumour biopsies in vitro. Int J Cancer. 1993 Jan 21;53(2):209–214. doi: 10.1002/ijc.2910530206. [DOI] [PubMed] [Google Scholar]
  9. Gasparini G., Bevilacqua P., Pozza F., Meli S., Boracchi P., Marubini E., Sainsbury J. R. Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer. Br J Cancer. 1992 Nov;66(5):970–976. doi: 10.1038/bjc.1992.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Green H. Terminal differentiation of cultured human epidermal cells. Cell. 1977 Jun;11(2):405–416. doi: 10.1016/0092-8674(77)90058-7. [DOI] [PubMed] [Google Scholar]
  11. Gullick W. J., Hughes C. M., Mellon K., Neal D. E., Lemoine N. R. Immunohistochemical detection of the epidermal growth factor receptor in paraffin-embedded human tissues. J Pathol. 1991 Aug;164(4):285–289. doi: 10.1002/path.1711640403. [DOI] [PubMed] [Google Scholar]
  12. Göppinger A., Wittmaack F. M., Wintzer H. O., Ikenberg H., Bauknecht T. Localization of human epidermal growth factor receptor in cervical intraepithelial neoplasias. J Cancer Res Clin Oncol. 1989;115(3):259–263. doi: 10.1007/BF00391699. [DOI] [PubMed] [Google Scholar]
  13. Haapasalo H., Isola J., Sallinen P., Kalimo H., Helin H., Rantala I. Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation. Am J Pathol. 1993 May;142(5):1347–1351. [PMC free article] [PubMed] [Google Scholar]
  14. Jiang L. W., Schindler M. Nucleocytoplasmic transport is enhanced concomitant with nuclear accumulation of epidermal growth factor (EGF) binding activity in both 3T3-1 and EGF receptor reconstituted NR-6 fibroblasts. J Cell Biol. 1990 Mar;110(3):559–568. doi: 10.1083/jcb.110.3.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kallioniemi O. P., Holli K., Visakorpi T., Koivula T., Helin H. H., Isola J. J. Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer. 1991 Nov 11;49(5):650–655. doi: 10.1002/ijc.2910490504. [DOI] [PubMed] [Google Scholar]
  16. Lee E. T., Desu M. M. A computer program for comparing K samples with right-censored data. Comput Programs Biomed. 1972 Nov;2(4):315–321. doi: 10.1016/0010-468x(72)90019-0. [DOI] [PubMed] [Google Scholar]
  17. Limas C., Bigler A., Bair R., Bernhart P., Reddy P. Proliferative activity of urothelial neoplasms: comparison of BrdU incorporation, Ki67 expression, and nucleolar organiser regions. J Clin Pathol. 1993 Feb;46(2):159–165. doi: 10.1136/jcp.46.2.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lipponen P. K., Eskelinen M. J., Jauhiainen K., Harju E., Terho R., Haapasalo H. Independent clinical, histological and quantitative prognostic factors in transitional-cell bladder tumours, with special reference to mitotic frequency. Int J Cancer. 1992 May 28;51(3):396–403. doi: 10.1002/ijc.2910510311. [DOI] [PubMed] [Google Scholar]
  19. Lipponen P. K. Histological and quantitative prognostic factors in transitional cell bladder cancer treated by cystectomy. Anticancer Res. 1992 Sep-Oct;12(5):1527–1532. [PubMed] [Google Scholar]
  20. Lipponen P. K., Nordling S., Eskelinen M. J., Jauhiainen K., Terho R., Harju E. Flow cytometry in comparison with mitotic index in predicting disease outcome in transitional-cell bladder cancer. Int J Cancer. 1993 Jan 2;53(1):42–47. doi: 10.1002/ijc.2910530109. [DOI] [PubMed] [Google Scholar]
  21. Lipponen P. K. Over-expression of p53 nuclear oncoprotein in transitional-cell bladder cancer and its prognostic value. Int J Cancer. 1993 Feb 1;53(3):365–370. doi: 10.1002/ijc.2910530304. [DOI] [PubMed] [Google Scholar]
  22. Lipponen P. Expression of c-erbB-2 oncoprotein in transitional cell bladder cancer. Eur J Cancer. 1993;29A(5):749–753. doi: 10.1016/s0959-8049(05)80360-0. [DOI] [PubMed] [Google Scholar]
  23. Massagué J. Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells. J Biol Chem. 1983 Nov 25;258(22):13614–13620. [PubMed] [Google Scholar]
  24. Merlo G. R., Bernardi A., Diella F., Venesio T., Cappa A. P., Callahan R., Liscia D. S. In primary human breast carcinomas mutations in exons 5 and 6 of the p53 gene are associated with a high S-phase index. Int J Cancer. 1993 Jun 19;54(4):531–535. doi: 10.1002/ijc.2910540402. [DOI] [PubMed] [Google Scholar]
  25. Moriyama M., Akiyama T., Yamamoto T., Kawamoto T., Kato T., Sato K., Watanuki T., Hikage T., Katsuta N., Mori S. Expression of c-erbB-2 gene product in urinary bladder cancer. J Urol. 1991 Feb;145(2):423–427. doi: 10.1016/s0022-5347(17)38356-8. [DOI] [PubMed] [Google Scholar]
  26. Neal D. E., Sharples L., Smith K., Fennelly J., Hall R. R., Harris A. L. The epidermal growth factor receptor and the prognosis of bladder cancer. Cancer. 1990 Apr 1;65(7):1619–1625. doi: 10.1002/1097-0142(19900401)65:7<1619::aid-cncr2820650728>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  27. Parker P. J., Young S., Gullick W. J., Mayes E. L., Bennett P., Waterfield M. D. Monoclonal antibodies against the human epidermal growth factor receptor from A431 cells. Isolation, characterization, and use in the purification of active epidermal growth factor receptor. J Biol Chem. 1984 Aug 10;259(15):9906–9912. [PubMed] [Google Scholar]
  28. Rakowicz-Szulczynska E. M., Rodeck U., Herlyn M., Koprowski H. Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3728–3732. doi: 10.1073/pnas.83.11.3728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ramael M., Segers K., Buysse C., Van den Bossche J., Van Marck E. Immunohistochemical distribution patterns of epidermal growth factor receptor in malignant mesothelioma and non-neoplastic mesothelium. Virchows Arch A Pathol Anat Histopathol. 1991;419(3):171–175. doi: 10.1007/BF01626344. [DOI] [PubMed] [Google Scholar]
  30. Sarkis A. S., Dalbagni G., Cordon-Cardo C., Zhang Z. F., Sheinfeld J., Fair W. R., Herr H. W., Reuter V. E. Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J Natl Cancer Inst. 1993 Jan 6;85(1):53–59. doi: 10.1093/jnci/85.1.53. [DOI] [PubMed] [Google Scholar]
  31. Schechter A. L., Hung M. C., Vaidyanathan L., Weinberg R. A., Yang-Feng T. L., Francke U., Ullrich A., Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. doi: 10.1126/science.2992090. [DOI] [PubMed] [Google Scholar]
  32. Tlsty T. D., White A., Sanchez J. Suppression of gene amplification in human cell hybrids. Science. 1992 Mar 13;255(5050):1425–1427. doi: 10.1126/science.1542791. [DOI] [PubMed] [Google Scholar]
  33. Ushiro H., Cohen S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J Biol Chem. 1980 Sep 25;255(18):8363–8365. [PubMed] [Google Scholar]
  34. Wright C., Mellon K., Johnston P., Lane D. P., Harris A. L., Horne C. H., Neal D. E. Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br J Cancer. 1991 Jun;63(6):967–970. doi: 10.1038/bjc.1991.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES