Acta Neurochirurgica

, Volume 138, Issue 12, pp 1399–1408 | Cite as

Outcome of 31 intracranial haemangiopericytomas: Poor predictive value of cell proliferation indices

  • V. Vuorinen
  • P. Sallinen
  • H. Haapasalo
  • T. Visakorpi
  • M. Kallio
  • J. Jääskeläinen
Clinical Articles


Cell proliferation indices of 31 primary intracranial haemangiopericytomas (HPC) and their recurrences and metastases were correlated with the long-term recurrence, metastasis and survival rates. Paraffin-embedded specimens were used for K-67, PCNA and p53 immunostainings and for estimation of S-phase fraction (S-PF) in flow cytometry. The median Ki-67 and PCNA indices and S-PFs were 10.4, 3.2, and 4.0 for primary HPCs and 14.1, 14.1, and 5.5 for recurrences, respectively. High indices were associated with higher recurrence, metastasis and death rates, but not at the p ≤ 0.5 level. Consequently, these indices do not seem useful in planning of treatment and follow-up of meningeal HPCs. Meningeal HPCs, in contrast to meningiomas, recur almost always despite seemingly complete removal and often metastasize elsewhere in the body. This difference between two sharply demarcated tumours must reflect particularly adhesive and infiltrative properties of HPC cells and not just higher proliferation potential.


Haemangiopericytoma intracranial outcome proliferation indices p53 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barbareschi M, Iuzzolino P, Pennella A, Allegranza A, Arrigoni G, Dalla Palma P, Doglioni C (1992) p53 protein expression in central nervous system neoplasms. J Clin Pathol 45: 583–586PubMedGoogle Scholar
  2. 2.
    Bastin KT, Mehta MP (1992) Meningeal hemangiopericytoma: defining the role for radiation therapy. J Neurooncol 14: 277–287PubMedGoogle Scholar
  3. 3.
    Bravo R (1986) Synthesis of the nuclear protein cyclin (PCNA) and its relationship with DNA replication. Exp Cell Res 163: 287–293PubMedGoogle Scholar
  4. 4.
    Bravo R, Frank R, Blundell PA, MacDonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase. Nature 326: 515–517PubMedGoogle Scholar
  5. 5.
    Cattoretti G, Becker MGH, Key G, Duchrow M, Schluter C, Galle J, Gerdes J (1992) Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB-1 and MIB-3) detect proliferating cells in microwave-processed formalin-fixed paraffin-embedded sections. J Pathol 168: 357–363PubMedGoogle Scholar
  6. 6.
    Chozick BS, Pezzulo JC, Epstein MH, Finch PW (1994) Prognostic implications of p53 overexpression in supratentorial astrocytic tumors. Neurosurgery 35: 831–837PubMedGoogle Scholar
  7. 7.
    Coffey RJ, Cascino TL, Shaw EG (1993) Radiosurgical treatment of recurrent hemangiopericytomas of the meninges: preliminary results. J Neurosurg 78: 903–908PubMedGoogle Scholar
  8. 8.
    Gushing H, Eisenhardt L (1938) Meningiomas, their classification, regional behaviour, life history, and end surgical results. Thomas, Springfield, pp 42–47Google Scholar
  9. 9.
    Deckert M, Reifenberger G, Wechsler W (1989) Determination of proliferative activity of human brain tumors using the monoclonal antibody Ki-67. J Cancer Res Clin Oncol 115: 179–188PubMedGoogle Scholar
  10. 10.
    Enzinger FM, Smith BH (1976) Hemangiopericytoma. An analysis of 106 cases. Hum Pathol 7: 61–82PubMedGoogle Scholar
  11. 11.
    Enzinger FM, Weiss SW (1988) Soft tissue tumors. Mosby, St. Louis, pp 596–613Google Scholar
  12. 12.
    Finn WG, Goolsby CL, Rao MS (1994) DNA flow cytometric analysis of hemangiopericytoma. Am J Clin Pathol 101: 181–185PubMedGoogle Scholar
  13. 13.
    Goellner JR, Laws ER, Soule EH, Okazaki H (1978) Hemangiopericytoma of the meninges. Mayo Clinic experience. Am J Clin Pathol 70: 375–380PubMedGoogle Scholar
  14. 14.
    Guthrie BL, Ebersold MJ, Scheithauer BW, Shaw EG (1989) Meningeal hemangiopericytoma: histopathological features, treatment, and long-term follow-up of 44 cases. Neurosurgery 25: 514–522PubMedGoogle Scholar
  15. 15.
    Haapasalo H, Isola J, Sallinen P, Kalimo H, Helin H, Rantala I (1993) Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation. Am J Pathol 142: 1347–1351PubMedGoogle Scholar
  16. 16.
    Hall PA, Levison DA, Woods AL, Yu CC-W, Kellock DB, Watkins JA, Barnes DM, Gillet CE, Camplejohn R, Dover R, Waseem NH, Lane DP (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162: 285–294PubMedGoogle Scholar
  17. 17.
    Heiden T, Wang N, Tribukait B (1991) An improved Hedley method for preparation of paraffin-embedded tissues for flow cytometric analysis of ploidy and S-phase. Cytometry 12: 614–621PubMedGoogle Scholar
  18. 18.
    Horten BC, Urich H, Rubinstein LJ, Montaque SR (1977) The angioblastic meningioma: a reappraisal of a nosological problem. Light-, electron-microscopic, tissue, and organ culture observations. J Neurol Sci 31: 387–410PubMedGoogle Scholar
  19. 19.
    Hsu DW, Hakim F, Biller BMK, de la Monte S, Zervas NT, Klibanski A, Hedley-Whyte ET (1993) Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg 78: 753–761PubMedGoogle Scholar
  20. 20.
    Hsu DW, Pardo FS, Efird JT, Linggood RM, Hedley-Whyte ET (1994) Prognostic significance of proliferative indices in meningiomas. J Neuropathol Exp Neurol 53: 247–255PubMedGoogle Scholar
  21. 21.
    Jellinger K, Slowik F (1975) Histological subtypes and prognostic problems in meningiomas. J Neurol 208: 279–298PubMedGoogle Scholar
  22. 22.
    Jääskeläinen J, Servo A, Haltia M, Wahlström T, Valtonen S (1985) Intracranial hemangiopericytoma: radiology, surgery, radiotherapy, and outcome in 21 patients. Surg Neurol 23: 227–236PubMedGoogle Scholar
  23. 23.
    Jääskeläinen J, Servo A, Haltia M, Kallio M, Troupp H (1991) Meningeal hemangiopericytoma. In: Schmidek H (ed) Meningiomas and their surgical treatment. Saunders, Orlando, pp 73–82Google Scholar
  24. 24.
    Kallio M, Sankila R, Hakulinen T, Jääkeläinen J (1992) Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Neurosurgery 31: 2–12PubMedGoogle Scholar
  25. 25.
    Kallioniemi O-P, Visakorpi T, Holli K, Heikkinen A, Isola J, Koivula T (1991) Improved prognostic impact of S-phase values from paraffin-embedded breast and prostate carcinomas after correcting for nuclear slicing. Cytometry 12: 413–421PubMedGoogle Scholar
  26. 26.
    Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304–6311PubMedGoogle Scholar
  27. 27.
    Kleihues P, Burger PC, Scheithauer BW (1991) World Health Organization International Histological Classification of Tumours: histological typing of tumours of the central nervous system. Springer, Berlin Heidelberg New York Tokyo, pp 38Google Scholar
  28. 28.
    Khoshyomn S, Maier H, Morimura T, Kitz K, Budka H (1993) Immunostaining for cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens. Acta Neuropathol 86: 582–589PubMedGoogle Scholar
  29. 29.
    Lane DP (1992) p53, guardian of the genome. Nature 358: 15–16PubMedGoogle Scholar
  30. 30.
    Lee KS, Hoshino T, Rodriguez LA (1990) Bromodeoxyuridine labeling study of intracranial meningiomas: proliferative potential and recurrence. Acta Neuropathol 80: 311–317PubMedGoogle Scholar
  31. 31.
    Maier H, Morimura T, Öfner D, Hallbrucker C, Kitz K, Budka H (1990) Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignancy and proliferation indices. Acta Neuropathol 80: 156–162PubMedGoogle Scholar
  32. 32.
    May PL, Broome JC, Lawry J, Buxton RA, Battersby RDE (1989) The prediction of recurrence in meningiomas. A flow cytometric study of paraffin-embedded archival material. J Neurosurg 71: 347–351PubMedGoogle Scholar
  33. 33.
    Mena H, Ribas JL, Pezeshkpour GH, Cowan DN, Parisi JE (1991) Hemangiopericytoma of the central nervous system: a review of 94 cases. Hum Pathol 22: 84–91PubMedGoogle Scholar
  34. 34.
    Morris GF, Mathews MB (1989) Regulation of proliferating cell nuclear antigen during the cell cycle. J Cell Biol 264: 13856–13864Google Scholar
  35. 35.
    Munakata S, Hendricks JB (1993) Effect of fixation time and microwave oven heating time on retrieval of the Ki-67 antigen from paraffin-embedded tissue. J Histochem Cytochem 41: 1241–1246PubMedGoogle Scholar
  36. 36.
    Ohta M, Iwaki T, Kitamoto T, Takeshita J, Fukui M (1994) MIB1 staining index and scoring of histologic features in meningioma. Indicators for the prediction of biological potential and postoperative management. Cancer 74: 3176–3189PubMedGoogle Scholar
  37. 37.
    Pitkethly DT, Hardman JM, Kempe LG, Earle KM (1970) Angioblastic meningiomas. Clinicopathologic study of 81 cases. J Neurosurg 32: 539–544PubMedGoogle Scholar
  38. 38.
    Roggendorf W, Schuster T, Peiffer J (1987) Proliferative potential of meningiomas determined with the monoclonal antibody Ki-67. Acta Neuropathol 73: 361–364PubMedGoogle Scholar
  39. 39.
    Russel DS, Rubinstein LJ (1991) Pathology of tumours of the nervous system. Edward Arnold, London, 474–479Google Scholar
  40. 40.
    Sallinen P, Haapasalo H, Kerttula T, Rantala I, Kalimo H, Collan Y, Isola J, Helin H (1994) Sources of variation in the assessment of cell proliferation using PCNA immunohistochemistry. Anal Quant Cytol Histol 16: 261–268PubMedGoogle Scholar
  41. 41.
    Sallinen PK, Haapasalo HH, Visakorpi T (1994) Prognostication of astrocytoma patient survival by Ki-67 (MIB-1), PCNA, and S-phase fraction using archival paraffin-embedded samples. J Pathol 174: 275–282PubMedGoogle Scholar
  42. 42.
    Sawwhney N, Hall PA (1992) Ki-67-structure, function, and new antibodies. J Pathol 168: 161–162PubMedGoogle Scholar
  43. 43.
    Schröder R, Firsching R, Kochanek S (1986) Hemangiopericytoma of meninges. II. General and clinical data. Zentralblatt Neurochir 47: 191–199Google Scholar
  44. 44.
    Shibuya M, Hoshino T, Ito S, Wacker MR, Prados MD, Davis RL, Wilson CB (1992) Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling. Neurosurgery 30: 494–498PubMedGoogle Scholar
  45. 45.
    Siitonen SM, Kallioniemi O-P, Isola J (1993) PCNA immunohistochemistry using MoAb 19A2 and new antigen retrieval has prognostic impact in archival paraffin embedded node-negative breast cancer. Am J Pathol 142: 1081–1090PubMedGoogle Scholar
  46. 46.
    Simpson D (1957) The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20: 22–39Google Scholar
  47. 47.
    Stout AP, Murray MR (1942) Hemangiopericytoma. A vascular tumor featuring Zimmermann's pericytes. Ann Surg 116: 26–33Google Scholar
  48. 48.
    Waseem NH, Lane DP (1990) Monoclonal antibody analysis of proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nuclear form. J Cell Sci 96: 121–129PubMedGoogle Scholar
  49. 49.
    Vojtesek B, Bartek J, Midgley CA, Lane DP (1992) An immunohistochemical analysis of human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151: 237–244PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • V. Vuorinen
    • 1
  • P. Sallinen
    • 2
  • H. Haapasalo
    • 3
  • T. Visakorpi
    • 4
  • M. Kallio
    • 2
  • J. Jääskeläinen
    • 1
  1. 1.Department of NeurosurgeryUniversity of HelsinskiFinland
  2. 2.Department of NeurologyUniversity of HelsinskiFinland
  3. 3.Department of PathologyUniversity of TampereFinland
  4. 4.Department of Clinical ChemistryUniversity of TampereFinland

Personalised recommendations