Skip to main content
Log in

Analysis of Proliferation and Apoptosis in Brain Gliomas: Prognostic and Clinical Value

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

Abstract

With the introduction of new (immuno-)histochemical techniques it is now possible to assess rates of proliferation and apoptosis in brain gliomas using archival paraffin embedded material. As proliferation and apoptosis are related to tumour growth rate quantification of these processes has prognostic value and is related to tumour grading. In this study we assessed the proliferation rate by measuring the Ki-67 labelling index using the MIB-1 antibody (MIB-LI) and the apoptotic rate using the in situ labelling of DNA strand breaks with TUNEL (TUNEL-LI) in 315 supratentorial gliomas. MIB-LI and TUNEL-LI in astrocytomas (A) where significantly lower compared to anaplastic astrocytomas (AA), glioblastomas (GBM) and oligodendroglial tumours [oligodendrogliomas (O) and anaplastic oligodendrogliomas (AO)]. MIB-LI and TUNEL-LI were significantly lower in AA compared to GBM. In astrocytic tumours MIB-LI and TUNEL-LI appeared to be correlated.

As the distinction between A and AA is of clinical value but can be difficult histomorphologically we analysed the prognostic value of MIB-LI and TUNEL-LI in gliomas with particular emphasis on A and AA. MIB-LI below 10% was of prognostic value in A and AA, O and AO but not in GBM on univariate survival analysis. TUNEL-LI was of no prognostic value. With multivariate survival analysis MIB-LI lost prognostic significance in O and AO. Astrocytomas with a gemistocytic component (AG) are similar to A with respect to survival and MIB-LI and TUNEL-LI. MIB-LI is of independent prognostic value in A and AA. Assessment of MIB-LI in A and AA can be used as an aid in distinguishing A and AA.

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

Access this article

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. Wakimoto H, Aoyagi M, Nakayama T, Nagashima G, Yamamoto S, Tamaki M, Hirakawa K: Prognostic significance of Ki-67 labelling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas. Cancer 77-2: 373–380, 1996

    Google Scholar 

  2. Schiffer D, Dutto A, Cavalla P, Bosone I, Chio A, Villani R, Belotti C: Prognostic factors in oligodendroglioma. Can J Neurol Sci 24-4: 313–319, 1997

    Google Scholar 

  3. Kros JM, Hop WC, Godschalk JJCJ, Krishnadath KK: Prognostic value of the proliferation related antigen Ki-67 in oligodendrogliomas. Cancer 78-5: 1107–1113, 1996

    Google Scholar 

  4. Schiffer D, Cavalla P, Chio A, Richaiardi P, Giordana MT: Proliferative activity and prognosis of low grade astrocytoma. J Neuro-Oncol 34: 31–35, 1997

    Google Scholar 

  5. Nakamura M, Konishi N, Tsunoda S, Hiasa Y, Tsuzuki T, Inui T, Sakaki T: Retinoblastoma protein expression and MIB-1 correlate with survival of patients with malignant astrocytoma. Cancer 80-2: 242–249, 1997

    Google Scholar 

  6. Schiffer D, Dutto A, Cavalla P, Chio A, Migheli A, Piva R: Role of apoptosis in the prognosis of oligodendrogliomas. Neurochem Int 31-2: 245–250, 1997

    Google Scholar 

  7. Hsu DW, Louis DN, Efird JT, Hedley-White ET: Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III gliomas. J Neuropath Exp Neurol 56-8: 857–865, 1997

    Google Scholar 

  8. Daumas Duport C, Scheithauer B, O'Fallon J, Kelly P: Grading of astrocytomas. A simple and reproducible method. Cancer 62: 2152–2165, 1988

    Google Scholar 

  9. Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK: Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 79-7: 1381–1393, 1997

    Google Scholar 

  10. Kleihues P, Burger PC, Scheithauer BW: The new WHO classification of brain tumors. Brain pathol 3: 255–268, 1993

    PubMed  Google Scholar 

  11. Going JJ: Efficiently estimated histologic cell counts. Hum Pathol 25: 333–336, 1994

    PubMed  Google Scholar 

  12. Davis RL, Onda K, Shubuya M, Lamborn K, Hoshino T: Proliferation markers in gliomas: a comparison of BUDR, Ki-67 and MIB-1. J Neuro-Oncol 24: 9–12, 1995

    Google Scholar 

  13. Onda K, Davis RL, Shibuya M, Wilson CB, Hoshino T: Correlation between the bromodeoxyuridine labeling index and the MIB-1 and Ki-67 proliferating cell indices in cerebral gliomas. Cancer 74-7: 1921–1926, 1994

    Google Scholar 

  14. Kordek R, Hironishi M, Liberski PP, Yanagihara R, Carleton Gajdusek D: Apoptosis in glial tumours as determined by in situ nonradioactive labeling of DNA breaks. Acta Neuropathol 91: 112–116, 1996

    PubMed  Google Scholar 

  15. Shoji Y, Saegusa M, Takano Y, Ohbu M, Okayasu I: Correlation of apoptosis with tumour cell differentiation, progression, and HPV infection in cervical carcinoma. J Clin Pathol 49: 134–138, 1996

    PubMed  Google Scholar 

  16. Van Slooten HJ, van de Vijver MJ, van de Velde CJH, van Dierendonck: Loss of bcl-2 in invasive breast cancer is associated with high rates of cell death, but also with increased proliferative activity. Br J Cancer 77-5: 789–796, 1998

    Google Scholar 

  17. Nakagawa S, Shiraishi T, Kihara S, Tabuchi K: Detection of DNA strand breaks associated with apoptosis in human brain tumors. Virchows Arch 427: 175–179, 1995

    PubMed  Google Scholar 

  18. Ellison DW, Steart PV, Gatter KC, Weller RO: Apoptosis in cerebral astrocytic tumours and its relationship to expression of the bcl-2 and p53 proteins. Neuropathol Appl Neurobiol 21: 352–361, 1995

    PubMed  Google Scholar 

  19. Evans G, Littlewood T: Apoptosis, a matter of life and cell death. Science 281: 1317–1322, 1998

    PubMed  Google Scholar 

  20. Shaw EG, Daumas-Duport C, Scheithauer BW, Gilbertson DT, O'Fallon JR, Earle JD, Laws JR, Okazaki H: Radiation therapy in the management of low grade supratentorial astrocytomas. J Neurosurg 70: 853–861, 1989

    PubMed  Google Scholar 

  21. North CA, North RB, Epstein JA, Piantadosi S, Wharam MD: Low grade cerebral astrocytomas. Survival and quality of life after radiation therapy. Cancer 66: 6–14, 1990

    PubMed  Google Scholar 

  22. Mornex F, Nayel H, Taillandier L: Radiation therapy for malignant astrocytomas in adults. Radiotherapy and Oncology 27: 181–191, 1993

    PubMed  Google Scholar 

  23. Winger MJ, Macdonald DR, Cairncross JG: Supratentorial anaplastic astrocytomas in adults. J Neurosurg 71: 487–493, 1993

    Google Scholar 

  24. Sheline GE: Radiotherapy for high grade gliomas. Int J Radiat Oncol Biol Phys 18: 793–803, 1990

    PubMed  Google Scholar 

  25. Ho DM, Wong T, Hsu C, Ting L, Chiang H: MIB-1 labelling index in nonpilocytic astrocytoma of childhood. Cancer 82-12: 2459–2466, 1998

    Google Scholar 

  26. Sallinen PK, Haapasalo HK, Visakorpi T, Helen PT, Rantala IS, Isola JJ, Helin HJ: Prognostication of astrocytoma patient survival by Ki-67 (Mib-1), PCNA, and S-phase fraction using archival paraffin-embedded samples. J Pathol 174: 275–282, 1994

    PubMed  Google Scholar 

  27. Krouwer HG, Davis RL, Silver P, Prados M: Gemistocytic astrocytomas: a reappraisal. J Neurosurg 74: 399–406, 1991

    PubMed  Google Scholar 

  28. Watanabe K, Tachibana O, Yonekawa Y, Kleihues P, Ohgaki H: Role of gemistocytes in astrocytoma progression. Lab Invest 76-2: 277–284, 1997

    Google Scholar 

  29. Karamitopoulou E, Perentes E, Diamantis I, Maraziotis T: Ki-67 immunoreactivity in human central nervous system tumours: a study with MIB-1 monoclonal antibody on archival material. Acta Neuropathol 87: 47–54, 1994

    PubMed  Google Scholar 

  30. Leighton C, Fisher B, Bauman G, Depiero S, Stitt L, Macdonald D, Cairncross G: Supratentorial low grade glioma in adults: an analysis of prognostic factors and timing of radiation. J Clin Oncol 15-4: 1294–1301, 1997

    Google Scholar 

  31. Schiffer D, Cavalla P, Migheli A, Chio A, Giordana MT, Marino S, Attanasio A: Apoptosis and cell proliferation in human neuroepithelial tumors. Neuroscience Letters 195: 81–84, 1995

    PubMed  Google Scholar 

  32. Coons SW, Johnson PC, Pearl DK: The prognostic significance of Ki-67 labeling indices for oligodendrogliomas. Neurosurgery 41-4: 878–884, 1997

    Google Scholar 

  33. Dehghani F, Schachenmayr AL, Laun A, Korf HW: Prognostic implication of histopathological, immunohistochemical and clinical features of oligodendrogliomas: a study of 89 cases. Acta Neuropathologica 95: 493–504, 1998

    PubMed  Google Scholar 

  34. Daumas-Duport C, Tucker ML, Kolles H, Cervera P, Beuvon F, Varlet P, Udo N, Koziak M, Chod kiewicz JP: Oligodendrogliomas. Part II: a new grading system based on morphological and imaging criteria. J Neuro-Oncol 34: 61–78, 1997

    Google Scholar 

  35. Cunningham JM, Kimmel DW, Scheithauer BW, O'Fallon JR, Novotny PJ, Jenkins RB: Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value. J Neurosurg 86: 121–130, 1997

    PubMed  Google Scholar 

  36. Kirkegaard LJ, De Rose PB, Yao B, Cohen C: Image cytometric measurement of nuclear proliferation markers (MIB-1, PCNA) in astrocytomas. Prognostic significance. Am J Clin Pathol 109-1: 69–74, 1998

    Google Scholar 

  37. Heegaard S, Sommer HM, Broholm H, Braendstrup O: Proliferating cell nuclear antigen and Ki-67 immunohistochemistry of oligodendrogliomas with special reference to prognosis. Cancer 76-10: 1809–1813, 1995

    Google Scholar 

  38. Wharton SB, Hamilton FA, Chant WK, Chan KK, Anderson JR: Proliferation and cell death in oligodendrogliomas. Neuropath Appl Neurobiol 24: 21–28, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heesters, M.A., Koudstaal, J., Go, K.G. et al. Analysis of Proliferation and Apoptosis in Brain Gliomas: Prognostic and Clinical Value. J Neurooncol 44, 255–266 (1999). https://doi.org/10.1023/A:1006398613605

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006398613605

Navigation