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Ki-67 immunoreactivity in human central nervous system tumors: a study with MIB 1 monoclonal antibody on archival material

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Abstract

Paraffin-embedded surgical specimens from 136 primary human central nervous system (CNS) tumors, including 50 meningiomas, 24 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 8 oligoden-drogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained, following microwave processing, using a streptavidin/peroxidase method and the MIB 1 monoclonal antibody (mAb) against the Ki-67 antigen. The following mean Ki-67 labeling index (LI) values ± SD were found: meningiomas, 2.47 ± 1.83; astrocytomas, 2.03 ± 2.03; anaplastic astrocytomas, 12.80 ± 6.29; glioblastomas, 14.57 ± 6.77; oligodendrogliomas, 5.06 ± 4.78; ependymomas, 2.63 ± 2.58; anaplastic ependymoma, 6.89; subependymomas, 1.79 ± 1.54; medulloblastomas, 18.77 ± 9.65; and paragangliomas, 2.19 ± 2.51. Our findings indicate that while malignant CNS tumors always exhibited high Ki-67 LI values, and benign CNS tumors generally displayed lower values, increased immunoreactivity for Ki-67 epitopes (Ki-67 LI higher than 4) was noted in a number of meningiomas, astrocytomas, ependymomas, oligodendrogliomas and paragangliomas, contrasting with their benign histological features. Further investigations of the Ki-67 immunoreactivity in CNS tumors and systematic correlation with the postoperative follow-up of patients are necessary to determine the value of Ki-67 LI in predicting the biological behavior of CNS neoplasms.

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References

  1. Allegranza A, Girlando S., Arrigoni GL, Veronese S, Mauri PA, Gambacorta M, Pollo B, Dalla Palma P, Barbareschi M (1991) Proliferating cell nuclear antigen expression in central nervous system neoplasms. Virchows Arch [A] 419: 417–423

    Google Scholar 

  2. Böker DK, Stark HJ (1988) The proliferation rate of intracranial tumors as defined by the monoclonal antibody Ki-67. Application of the method to paraffin-embedded specimens. Neurosurg Rev 11: 267–272

    PubMed  Google Scholar 

  3. Böker DK, Stark HJ, Gullotta F, Nadstawek J, Schultheiss R (1990) Immunohistochemical demonstration of the Ki-67-antigen in paraffin-embedded tumor biopsies. Clin Neuropathol 9: 51–54

    PubMed  Google Scholar 

  4. Burger PC, Shibata T, Kleihues P (1986) 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

    PubMed  Google Scholar 

  5. Burger PC, Rawlings CE, Cox EB, McLendon RE, Schold SC Jr, Bullard DE (1987) Clinicopathologic correlations in the oligodendroglioma. Cancer 59: 1345–1352

    PubMed  Google Scholar 

  6. Burger PC, Scheithauer BW, Vogel FS (1991) Surgical pathology of the nervous system and its coverings, 3rd edn. Churchill Livingstone, New York, pp 25–27, 650–653

    Google Scholar 

  7. Burns DK, Mickey BE, Bigio EH, White CL (1992) Proliferating cell nuclear antigen (PCNA) expression in human gliomas and meningiomas (abstract). J Neuropathol Exp Neurol 51: 362

    Google Scholar 

  8. Cattoretti G, Becker MHG, Key G, Duchrow M, Schlüter C, Galle J, Gerdes J (1992) Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB1 and MIB3) detect proliferating cells in microwave-processed formalinfixed paraffin sections. J Pathol 168: 357–363

    PubMed  Google Scholar 

  9. 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 

  10. Dumouchel W (1987) A data analysis advisor. Technical Report, BBN Software Products Corporation, Cambridge, Mass

    Google Scholar 

  11. Fukui M, Iwaki T, Sawa H, Inoue T, Takeshita I, Kitamura K (1986) Proliferative activity of meningiomas as evaluated by bromodeoxyuridine uptake examination. Acta Neurochir (Wien) 81: 135–141

    Google Scholar 

  12. 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 

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

    PubMed  Google Scholar 

  14. Gerdes J, Lemke H, Baisch H, Wacker HH, 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 

  15. Gerdes J, Lelle RJ, Pickartz H, Heidenreich W, Schwarting R, Kurtsiefer L, Stauch G, Stein H (1986) Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. J. Clin Pathol 39: 977–980

    PubMed  Google Scholar 

  16. Gerdes J, Li L, Schlueter C, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138: 867–873

    PubMed  Google Scholar 

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

    Google Scholar 

  18. Hall PA, Woods AL (1990) Immunohistochemical markers of cellular proliferation: achievements, problems and prospects. Cell Tissue Kinet 23: 505–522

    PubMed  Google Scholar 

  19. Hall PA, Richards MA, Gregory WM, d'Ardenne AJ, Lister TA, Stansfield AG (1988) The prognostic value of Ki-67 immunostaining in non-Hodgkin's lymphoma. J Pathol 154: 223–235

    PubMed  Google Scholar 

  20. Hara A, Hirayama H, Sakai N, Yamada H, Tanaka T, Mori H (1991) Nucleolar organizer region score and Ki-67 labelling index in high-grade gliomas and metastatic brain tumors. Acta Neurochir (Wien) 109: 37–41

    Google Scholar 

  21. Hoaglin DC, Mosteller F, Tukey JW (1983) Understanding robust and exploratory data analysis. John Wiley and Sons, New York

    Google Scholar 

  22. Hoshino T, Wilson CB (1979) Cell kinetic analysis of human malignant brain tumors (gliomas). Cancer 44: 956–962

    PubMed  Google Scholar 

  23. Hoshino T, Nagashima T, Murovic JA, Wilson CB, Edwards MSB, Gutin PH, Davis RL, De Armond SJ (1986) In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling. J Neurosurg 64: 453–459

    PubMed  Google Scholar 

  24. Hoshino T, Nagashima T, Murovic JA, Wilson CB, Davis RL (1986) Proliferative potential of human meningiomas of the brain: a cell kinetic study with bromodeoxyuridine. Cancer 58: 1466–1472

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  26. Karamitopoulou E, Perentes E, Melachrinou M, Maraziotis T (1993) Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms. Acta Neuropathol 85: 316–322

    PubMed  Google Scholar 

  27. Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumours. Brain Pathol 3: 255–268

    PubMed  Google Scholar 

  28. Labrousse F, Daumas-Duport C, Batorski L, Hoshino T (1991) Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases. J Neurosurg 75: 202–205

    PubMed  Google Scholar 

  29. Lee KS, Hoshino T, Rodriguez LA, Bederson J, Davis RL, Wilson CB (1990) Bromodeoxyuridine labeling study of intracranial meningiomas: proliferative potential and recurrence. Acta Neuropathol 80: 311–317

    PubMed  Google Scholar 

  30. Louis DN, Edgerton S, Thor AD, Hedley-Whyte ET (1991) Proliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: a comparative study. Acta Neuropathol 81: 675–679

    PubMed  Google Scholar 

  31. Maier H, Morimura T, Öfner D, Hallbrucker C, Kitz K, Budka H (1990) Argyrophilic nucleolar organizer region proteins (AgNORs) in human brain tumors: relations with grade of malignancy and proliferation indices. Acta Neuropathol (Berl) 80: 156–162

    Google Scholar 

  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: 347–351

    PubMed  Google Scholar 

  33. McGurrin JF, Doria MI, Dawson PJ, Karrison T, Stein HO, Franklin WA (1987) Assessment of tumor cell kinetics by immunohistochemistry in carcinoma of breast. Cancer 59: 1744–1750

    PubMed  Google Scholar 

  34. Morimura T, Kitz K, Budka H (1989) 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

    PubMed  Google Scholar 

  35. Nagashima T, DeArmond SJ, Murovic J, Hoshino T (1985) Immunocytochemical demonstration of S-phase cells by antibromodeoxyuridine monoclonal antibody in human brain tumor tissues. Acta Neuropathol (Berl) 67: 155–159

    Google Scholar 

  36. Nishizaki T, Orita T, Saiki M, Furutani Y, Aoki H (1988) Cell kinetics studies of human brain tumors by in vitro labeling using anti-BUdR monoclonal antibody. J Neurosurg 69: 371–374

    PubMed  Google Scholar 

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

    Google Scholar 

  38. 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 

  39. Plate KH, Rueschoff J, Behnke J, Mennel HD (1990) Proliferative potential of human brain tumors as assessed by nucleolar organizer regions (Ag NORs) and Ki-67 immunoreactivity. Acta Neurochir (Wien) 104: 103–109

    Google Scholar 

  40. Raghavan R, Steart PV, Weller RO (1990) Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study. Neuropathol Appl Neurobiol 16: 123–133

    PubMed  Google Scholar 

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

    Google Scholar 

  42. Schröder R, Bien K, Kott R, Meyers I, Vössing R (1991) The relationship between Ki-67 labeling and mitotic index in gliomas and meningiomas: demonstration of the variability of the intermitotic cycle time. Acta Neuropathol 82: 389–394

    PubMed  Google Scholar 

  43. Shaw EG, Scheithauer BW, O'Fallon JR, Tazelaar HD, Davis DH (1992) Oligodendrogliomas: the Mayo Clinic experience. J Neurosurg 76: 428–434

    PubMed  Google Scholar 

  44. Shepherd NA, Richman PI, England J (1988) Ki-67 derived proliferative activity in colorectal adenocarcinoma with prognostic correlations. J Pathol 155: 213–219

    PubMed  Google Scholar 

  45. Shibuya M, Ito S, Miwa T, Davis RL, Wilson CB, Hoshino T (1993) Proliferative potential of brain tumors. Analyses with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts. Cancer 71: 199–206

    PubMed  Google Scholar 

  46. Siegers HP, Zuber P, Hamon MF, Van Melle GD, de Tribolet N (1989) The implications of the heterogeneous distribution of Ki-67 labelled cells in meningiomas. Br J Neurosurg 3: 101–108

    PubMed  Google Scholar 

  47. Swanson SA, Brooks JJ (1990) Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics. Am J Pathol 137: 1491–1500

    PubMed  Google Scholar 

  48. Yonemura Y, Kimura H, Ooyama S, Kamata T, Yamaguchi A, Matsumoto H, Ninomiya I, Miyazaki I (1991) Immunocytochemical staining of proliferating cells in endoscopically biopsied tissues of gastric carcinomas with monoclonal antibody Ki-67. Oncology 48: 162–165

    PubMed  Google Scholar 

  49. Yoshii Y, Maki Y, Tsuboi K, Tumono Y, Nakagawa K, Hoshino T (1986) Estimation of growth fraction with bromodeoxyuridine in human central nervous system tumors. J Neurosurg 65: 659–663

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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Karamitopoulou, E., Perentes, E., Diamantis, I. et al. Ki-67 immunoreactivity in human central nervous system tumors: a study with MIB 1 monoclonal antibody on archival material. Acta Neuropathol 87, 47–54 (1994). https://doi.org/10.1007/BF00386253

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  • DOI: https://doi.org/10.1007/BF00386253

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