Skip to main content
SpringerLink
Log in

Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas

  • Neuropathological Articles
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Summary

The aim of this study was to determine possible relationships between Ki-67 labelling index (Ki-67 LI), amplification of the epidermal growth factor receptor (EGFR) gene, and prognosis in human glioblastomas. Ki-67 LI was determined on cryosections of biopsy specimens of 20 human glioblastomas with a mouse antihuman Ki-67 monoclonal antibody. Amplification of the EGFR gene was determined by slot blot and Southern blot analyses of DNA extracted from the tumour biopsies. The Ki-67 LI was higher in the glioblastoma group with EGFR gene amplification (8 tumours, median value of Ki-67 LI 4.2, range 0.4–24.6) than in those without EGFR gene amplification (12 tumours, median value of Ki-67 LI 0.8, range 0.2–11.8) (0.05 p<0.1). The glioblastoma patients with Ki-67 LI>1.5 (10 tumours) had a statistically significant shorter survival than those with Ki-67 LI<1.5 (10 tumours) (p<0.05). The glioblastoma patients with EGFR gene amplification lived shorter time than those without EGFR gene amplification (p>0.05).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aasland R, Olsen LC, Spurr NK, Krokan HE, Helland DE (1990) Chromosomal assignment of human uracil-DNA glycosylase to chromosome 12. Genomics 7: 139–141

    PubMed  Google Scholar 

  2. Bigner SH, Burger PC, Wong AJ, Werner MH, Hamilton SR, Muhlbaier LH, Vogelstein B, Bigner DD (1988) Gene amplification in malignant human gliomas: clinical and histopathologic aspects. J Neuropathol Exp Neurol 47: 191–205

    PubMed  Google Scholar 

  3. Brown DC, Gatter KC (1990) Monoclonal antibody Ki-67: its use in histopathology. Histopathol 17: 489–503

    Google Scholar 

  4. Burger PC, Shibata T, Kleihues P (1988) Proliferation markers for neoplasms of the nervous system. In: DeLellis RA (eds) Advances in immunohistochemistry. Raven Press, New York, pp 301–316

    Google Scholar 

  5. Church GM, Gilbert W (1984) Genomic sequencing. Proc Acad Natl Sci USA 81: 1991–1995

    Google Scholar 

  6. Deckert M, Reifenberger G, Wechsler W (1989) Determination of the proliferative potential of human brain tumors using the monoclonal antibody Ki-67. J Cancer Res Clin Oncol 115: 179–188

    PubMed  Google Scholar 

  7. Downs TR, Wilfinger WW (1983) Fluorometric quantification of DNA in cells and tissue. Analyt Biochem 131: 538–547

    PubMed  Google Scholar 

  8. Ekstrand AJ, James CD, Cavenee WK, Seliger B, Petterson RF, Collins VP (1991) Genes for epidermal growth factor receptor, transforming growth factor α, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 51: 2164–2172

    PubMed  Google Scholar 

  9. Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31: 13–20

    PubMed  Google Scholar 

  10. Gerdes J, Lemke H, Baisch H, Wacker H-H, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133: 1710–1715

    PubMed  Google Scholar 

  11. Giangaspero F, Doglioni C, Rivano MT, Pileri S, Gerdes J, Stein H (1987) Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67. Acta Neuropathol (Berl) 74: 179–182

    Google Scholar 

  12. Helseth E, Unsgaard G, Dalen A, Fure H, Skandsen T, Ødegaard A, Vik R (1988) Amplification of the epidermal growth factor receptor gene in biopsy specimens from human intracranial tumours. Br J Neurosurg 2: 217–225

    PubMed  Google Scholar 

  13. Helseth E, Brøgger A, Dalen A, Fure H, Greff Johansen S, Eknæs Lier M, Skandsen T, Unsgaard G, Vik R (1990) Polysomy of chromosome 7 is associated with amplification and overexpression of the EGF-receptor gene in a human carcinoma cell line derived from a brain metastasis. APMIS 98: 996–1004

    PubMed  Google Scholar 

  14. Hoshino T, Prados M, Wilson CB, Cho KG, Lee K-S, Davis RL (1989) Prognostic implications of the bromodeoxyuridine labeling index of human gliomas. J Neurosurg 71: 335–341

    PubMed  Google Scholar 

  15. Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H (1984) Expression of epidermal growth factor receptors in human brain tumours. Cancer Res 44: 753–760

    PubMed  Google Scholar 

  16. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J (1985) Amplification, enhanced expression, and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313: 144–147

    PubMed  Google Scholar 

  17. Maruno M, Kovach JS, Kelly PJ, Yanagihara T (1991) Transforming growth factor-α, epidermal growth factor receptor, and proliferating potential in benign and malignant gliomas. J Neurosurg 75: 97–102

    PubMed  Google Scholar 

  18. Morimura T, Kitz K, Stein H, Budka H (1991) Determination of proliferative activities in human brain tumour specimens: a comparison of three methods. J Neuro=Oncol 10: 1–11

    Google Scholar 

  19. Olsen LC, Aasland R, Wittwer CU, Krokan HE, Helland DE (1989) Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme. EMBO J 8: 3121–3125

    PubMed  Google Scholar 

  20. Ostertag CB, Volk B, Shibata T, Burger P, Kleihues P (1987) The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours. Acta Neurochir (Wien) 89: 117–121

    Google Scholar 

  21. Patsouris E, Stocker U, Kallmeyer V, Keiditsch E, Mehraein P, Stavrou D (1988) Relationship between Ki-67 positive cells, growth rate, and histological type of human intracranial tumors. Anticancer Res 8: 537–544

    PubMed  Google Scholar 

  22. Pigott TJD, Lowe JS, Palmer J (1991) Statistical modelling in analysis of prognosis in glioblastoma multiforme: a study of clinical variables and Ki-67 index. Br J Neurosurg 5: 61–66

    PubMed  Google Scholar 

  23. Quinn CM, Wright NA (1990) The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol 160: 93–102

    PubMed  Google Scholar 

  24. Torp SH, Helseth E, Dalen A, Unsgaard G (1991) Epidermal growth factor receptor expression in human gliomas. Cancer Immunol Immunother 33: 61–64

    PubMed  Google Scholar 

  25. Velu TJ (1990) Structure, function, and transforming potential of the epidermal growth factor receptor. Mol Cell Endocrinol 70: 205–216

    PubMed  Google Scholar 

  26. Xu Y-H, Ishii S, Clark AJL, Sullivan M, Wilson RK, Ma DP, Roe BA, Merlino GT, Pastan I (1984) Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells. Nature 309: 806–810

    PubMed  Google Scholar 

  27. Zuber P, Hamou M-F, de Tribolet N (1988) Identification of proliferating cells in human gliomas using the monoclonal antibody Ki-67. Neurosurgery 22: 364–368

    PubMed  Google Scholar 

  28. Zülch KJ (1979) Histological typing of tumours of the central nervous system. In: International Histological Classification of Tumours, No 21. World Health Organization, Geneva

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Technical Centre, Institute of Cancer Research, Trondheim

    S. H. Torp

  2. Department of Neurosurgery, University Hospital of Trondheim, Trondheim, Norway

    E. Helseth & G. Unsgaard

  3. Department of Microbiology, University Hospital of Trondheim, Trondheim, Norway

    A. Dalen

Authors
  1. S. H. Torp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Helseth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Dalen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Unsgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torp, S.H., Helseth, E., Dalen, A. et al. Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas. Acta neurochir 117, 182–186 (1992). https://doi.org/10.1007/BF01400618

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01400618

Keywords

Search

Navigation