Skip to main content
SpringerLink
Log in

Determination of proliferative activities in human brain tumor specimens: a comparison of three methods

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

Proliferative activities were determined in 72 human brain tumors, including 20 metastatic carcinomas, 41 gliomas, 8 meningiomas and 3 hematological tumors. Immunocytochemical techniques included labeling with monoclonal antibody (mAb) to bromodeoxyuridine (BrdU) which identifies S phase cells after previous in vitro BrdU incubation and paraffin embedding of fixed tissue specimens, and with mAb Ki-67 which reacts, in frozen sections, with a nuclear antigen expressed by all proliferating cells. BrdU labeling index (LI), Ki-67 LI and mitotic index (MI) correlated well with histological malignancy. Among the three proliferation indices, Ki-67 LI and BrdU LI were highly significantly correlated. With the exception of hematological malignancies, hyperbaric oxygenation of in vitro BrdU labeling did not significantly increase BrdU LI or depth of BrdU penetration into tissue. This study indicates that in vitro BrdU labeling is a useful alternative to Ki-67 immunolabeling of human brain tumor specimens. By such determination of tumor proliferation, it might be possible to design a more adequate postoperative therapy tailored to patients individually.

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. Baserga R: The cell cycle. N Eng J Med 304: 453–459, 1981

    Google Scholar 

  2. Burger PC, Shibata T, Kleihues P: The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: Application to surgical neuropathology. Am J Surg Pathol 10: 611–617, 1986

    Google Scholar 

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

    Google Scholar 

  4. Fabrikant JI, Wisseman III CL, Vitak MJ: The kinetics of cellular proliferation in normal and malignant tissues. II. An in vitro method for incorporation of tritiated thymidine in human tissues. Radiology 192: 1309–1320, 1969

    Google Scholar 

  5. Falini B, Canino S, Sacchi S, et al.: Immunocytochemical evaluation of the percentage of proliferating cells in pathological bone marrow and peripheral blood samples with the Ki-67 and anti-bromo-deoxyuridine monoclonal antibodies. Br J Haematol 69: 311–320, 1988

    Google Scholar 

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

    Google Scholar 

  7. Gerdes J, Dallenbach F, Lennert K: Growth fractions in malignant non-Hodgkin' lymphomas (NHL) as determined in situ with the monoclonal antibody Ki-67. Haematol Oncol 2: 365–371, 1984

    Google Scholar 

  8. Giangaspero F, Doglioni C, Riavino MT, et al.: Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67. Acta Neuropathol 74: 179–182, 1987

    Google Scholar 

  9. Graem N, Helweg-Larsen K: Mitotic activity and delay in fixation of tumor tissue. Acta Pathol Microbiol Scand A 87: 375–378,1979

    Google Scholar 

  10. Gratzner HG: Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science 218: 474–475, 1982

    Google Scholar 

  11. Hirst DG, Denekamp J, Hobson B: Proliferation kinetics of endothelial and tumor cells in 3 mouse mammary carcinomas. Cell Tissue Kinet 15: 251–261, 1982

    Google Scholar 

  12. Hoshino T, Nagashima T, Cho KG, et al.: S-phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine. Int J Cancer 38: 369–374, 1986

    Google Scholar 

  13. Hoshino T, Nagashima T, Murovic JA, et al.: Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine. Cancer 58: 1466–1472, 1986

    Google Scholar 

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

    Google Scholar 

  15. Hsu S-M, Raine L, Fauger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedure. J Histochem Cytochem 29: 577–580, 1981

    Google Scholar 

  16. Johnson HA: Some problems associated with the histological study of cell proliferation kinetics. Cytologia 26: 32–41, 1961

    Google Scholar 

  17. Kernohan JW, Mabon RF, Svien HJ, et al.: Symposium on a new and simplified concept of gliomas (a simplified classification of gliomas). Proc Mayo Clin 24: 71–75, 1949

    Google Scholar 

  18. Lellè RJ, Heidenreich W, Stauch G, et al.: The correlation of growth fractions with histologic grading and lymph nodes status in human mammary carcinoma. Cancer 59: 83–88, 1987

    Google Scholar 

  19. Meyer JS, Bauer WC: In vitro determination of tritiated thymidine labeling index (LI): Evaluation of a method utilizing hyperbaric oxygen and observations on the LI of human mammary carcinoma. Cancer 36: 1374–1380, 1975

    Google Scholar 

  20. Molnar P, Groothuis D, Blasberg R, et al.: Regional thymidine transport and incorporation in experimental brain and subcutaneous tumors. J Neurochem 43: 421–432, 1984

    Google Scholar 

  21. Morimura T, Kitz K, Budka H: In situ analysis of cell kinetics in human brain tumors: A comparative immunocytochemical study of S phase cells by a new in vitro bromodeoxyuridine-labeling technique, and of proliferating pool cells by monoclonal antibody Ki-67. Acta Neuropathol 77: 276–282,1989

    Google Scholar 

  22. Nagashima T, DeArmond SJ, Murovic J, et al.: Immunocytochemical demonstration of S-phase cells by anti-bromodeoxyuridine monoclonal antibody in human brain tumor tissues. Acta Neuropathol 67: 155–159, 1985

    Google Scholar 

  23. Nishizaki T, Orita T, Saiki M, et al.: Cell kinetics studies of human brain tumors by in vitro labeling using anti-BrdU monoclonal antibody. J Neurosurg 69: 371–374, 1988

    Google Scholar 

  24. Nishizaki T, Orita T, Furutani Y, et al.: Flow-cytometric DNA analysis and immunocytochemical measurement of Ki-67 and BrdU labeling indices in human brain tumors. J Neurosurg 70: 379–384, 1989

    Google Scholar 

  25. Ostertag CB, Volk B, Shibata T, et al.: The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumors. Acta Neurochir 89: 117–121,1987

    Google Scholar 

  26. Roggendorf W, Schuster T, Peiffer J: Proliferative potential of meningiomas determined with the monoclonal antibody Ki-67. Acta Neuropathol 73: 361–364, 1987

    Google Scholar 

  27. Sasaki K, Ogino T, Takahashi M: Immunological determination of labeling index on human tumor tissue sections using monoclonal anti-BrdUrd antibody. Stain Technol 61: 155–161,1986

    Google Scholar 

  28. Sasaki K, Matsumura K, Tsuji T, et al.: Relationship between labeling indices of Ki-67 and BruUrd in human malignant tumors. Cancer 62: 989–993, 1988

    Google Scholar 

  29. Steel GG, Bensted JPM: In vitro studies of cell proliferation in tumors. I. Critical appraisal of methods and theoretical considerations. Eur J Cancer 1: 275–279, 1965

    Google Scholar 

Download references

Author information

Author notes

  1. Tatsuo Morimura

    Present address: Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan

Authors and Affiliations

  1. Neurological Institute, University of Vienna, Schwarzspanierstr. 17, A-1090, Wien, Austria

    Tatsuo Morimura & Herbert Budka

  2. Neurosurgical Clinic, University of Vienna, Austria

    Klaus Kitz

  3. Institute of Pathology, Free University of Berlin, FRG

    Harald Stein

Authors
  1. Tatsuo Morimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Kitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harald Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Herbert Budka
    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

Morimura, T., Kitz, K., Stein, H. et al. Determination of proliferative activities in human brain tumor specimens: a comparison of three methods. J Neuro-Oncol 10, 1–11 (1991). https://doi.org/10.1007/BF00151242

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00151242

Key words

Search

Navigation