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Logo of jnnpsycJournal of Neurology, Neurosurgery and PsychiatryCurrent TOCInstructions for authors
J Neurol Neurosurg Psychiatry. Oct 1995; 59(4): 413–419.
PMCID: PMC486079

Prognostic indicators in a range of astrocytic tumours: an immunohistochemical study with Ki-67 and p53 antibodies.

Abstract

The treatment and prognosis of patients with cerebral astrocytic tumours are currently guided by histopathological classification. This study evaluates immunohistochemistry using Ki-67, an antibody to a nuclear protein expressed in proliferating cells, and DO-7, an antibody to the product of the tumour suppressor gene p53, as prognostic indicators for these tumours. Immunohistochemistry with Ki-67 has been correlated with the behaviour of many different tumours, but its value as a prognostic indicator in astrocytic tumours is diminished by the conflicting results of previous studies. Immunohistochemistry with antibodies to the p53 protein has been used as a prognostic indicator in melanomas and some carcinomas, but the relation between prognosis and accumulation of this protein in astrocytic tumours has not been clarified. We have tested the hypothesis that survival is correlated with Ki-67 immunolabelling indices (LIs) and patterns of p53 immunolabelling in the cerebral astrocytic tumours of a large cohort of patients (n = 123) for whom clinical indices were well documented. Astrocytic tumours were divided into three histological types: fibrillary astrocytoma (n = 24), anaplastic astrocytoma (n = 31), and glioblastoma (n = 68). Histological type and patient age were independent predictors of survival. Median Ki-67 LIs differed significantly (P < 0.0001) between the types of astrocytic tumour, and tumours with a Ki-67 LI < 2% had a significantly (P < 0.0001) better prognosis. Ki-67 LI as a continuous variable carried a significant (P = 0.0043) unadjusted hazard to survival which was lost when adjusted for other variables, notably histological type. By contrast, no relation was found between survival and three categories of p53 labeling (p53-negative, p53 LI < 40%, and p53 LI > 60%). The results indicate that, whereas Ki-67 immunohistochemistry predicts survival in patients with astrocytic tumours, conventional histological appraisal remains the best guide to prognosis, and immunohistochemistry for p53 has no value in the assessment of these tumours.

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Selected References

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  • VandenBerg SR. Current diagnostic concepts of astrocytic tumors. J Neuropathol Exp Neurol. 1992 Nov;51(6):644–657. [PubMed]
  • Burger PC, Vogel FS, Green SB, Strike TA. Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer. 1985 Sep 1;56(5):1106–1111. [PubMed]
  • Ellison DW, Weller RO. Forecasting the prognosis of a patient with a tumour. Neuropathol Appl Neurobiol. 1992 Dec;18(6):626–627. [PubMed]
  • Louis DN, Edgerton S, Thor AD, Hedley-Whyte ET. Proliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: a comparative study. Acta Neuropathol. 1991;81(6):675–679. [PubMed]
  • 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. 1989;77(3):276–282. [PubMed]
  • Raghavan R, Steart PV, Weller RO. Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study. Neuropathol Appl Neurobiol. 1990 Apr;16(2):123–133. [PubMed]
  • Gerdes J, Li L, Schlueter C, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD. Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol. 1991 Apr;138(4):867–873. [PMC free article] [PubMed]
  • Brown DC, Gatter KC. Monoclonal antibody Ki-67: its use in histopathology. Histopathology. 1990 Dec;17(6):489–503. [PubMed]
  • Cattoretti G, Becker MH, Key G, Duchrow M, Schlüter C, Galle J, Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992 Dec;168(4):357–363. [PubMed]
  • Jaros E, Perry RH, Adam L, Kelly PJ, Crawford PJ, Kalbag RM, Mendelow AD, Sengupta RP, Pearson AD. Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours. Br J Cancer. 1992 Aug;66(2):373–385. [PMC free article] [PubMed]
  • Zuber P, Hamou MF, de Tribolet N. Identification of proliferating cells in human gliomas using the monoclonal antibody Ki-67. Neurosurgery. 1988 Feb;22(2):364–368. [PubMed]
  • Barnes DM, Dublin EA, Fisher CJ, Levison DA, Millis RR. Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis? Hum Pathol. 1993 May;24(5):469–476. [PubMed]
  • McGregor JM, Yu CC, Dublin EA, Barnes DM, Levison DA, MacDonald DM. p53 immunoreactivity in human malignant melanoma and dysplastic naevi. Br J Dermatol. 1993 Jun;128(6):606–611. [PubMed]
  • Quinlan DC, Davidson AG, Summers CL, Warden HE, Doshi HM. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res. 1992 Sep 1;52(17):4828–4831. [PubMed]
  • Thomas DJ, Robinson M, King P, Hasan T, Charlton R, Martin J, Carr TW, Neal DE. p53 expression and clinical outcome in prostate cancer. Br J Urol. 1993 Nov;72(5 Pt 2):778–781. [PubMed]
  • Fields S, Jang SK. Presence of a potent transcription activating sequence in the p53 protein. Science. 1990 Aug 31;249(4972):1046–1049. [PubMed]
  • Lane DP. The regulation of p53 function: Steiner Award Lecture. Int J Cancer. 1994 Jun 1;57(5):623–627. [PubMed]
  • Marx J. How p53 suppresses cell growth. Science. 1993 Dec 10;262(5140):1644–1645. [PubMed]
  • Prives C. Doing the right thing: feedback control and p53. Curr Opin Cell Biol. 1993 Apr;5(2):214–218. [PubMed]
  • Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature. 1993 Apr 29;362(6423):849–852. [PubMed]
  • Kern SE, Pietenpol JA, Thiagalingam S, Seymour A, Kinzler KW, Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science. 1992 May 8;256(5058):827–830. [PubMed]
  • Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523–526. [PubMed]
  • Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 1993 Jul;7(7A):1126–1132. [PubMed]
  • Louis DN. The p53 gene and protein in human brain tumors. J Neuropathol Exp Neurol. 1994 Jan;53(1):11–21. [PubMed]
  • Reifenberger G, Liu L, Ichimura K, Schmidt EE, Collins VP. Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 1993 Jun 15;53(12):2736–2739. [PubMed]
  • Rubio MP, von Deimling A, Yandell DW, Wiestler OD, Gusella JF, Louis DN. Accumulation of wild type p53 protein in human astrocytomas. Cancer Res. 1993 Aug 1;53(15):3465–3467. [PubMed]
  • Ellison DW, Gatter KC, Steart PV, Lane DP, Weller RO. Expression of the p53 protein in a spectrum of astrocytic tumours. J Pathol. 1992 Dec;168(4):383–386. [PubMed]
  • Barbareschi M, Iuzzolino P, Pennella A, Allegranza A, Arrigoni G, Dalla Palma P, Doglioni C. p53 protein expression in central nervous system neoplasms. J Clin Pathol. 1992 Jul;45(7):583–586. [PMC free article] [PubMed]
  • Haapasalo H, Isola J, Sallinen P, Kalimo H, Helin H, Rantala I. Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation. Am J Pathol. 1993 May;142(5):1347–1351. [PMC free article] [PubMed]
  • Burger PC, Green SB. Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer. 1987 May 1;59(9):1617–1625. [PubMed]
  • Cohadon F, Aouad N, Rougier A, Vital C, Rivel J, Dartigues JF. Histologic and non-histologic factors correlated with survival time in supratentorial astrocytic tumors. J Neurooncol. 1985;3(2):105–111. [PubMed]
  • Kim TS, Halliday AL, Hedley-Whyte ET, Convery K. Correlates of survival and the Daumas-Duport grading system for astrocytomas. J Neurosurg. 1991 Jan;74(1):27–37. [PubMed]
  • Onda K, Davis RL, Wilson CB, Hoshino T. Regional differences in bromodeoxyuridine uptake, expression of Ki-67 protein, and nucleolar organizer region counts in glioblastoma multiforme. Acta Neuropathol. 1994;87(6):586–593. [PubMed]
  • Karamitopoulou E, Perentes E, Diamantis I. p53 protein expression in central nervous system tumors: an immunohistochemical study with CM1 polyvalent and DO-7 monoclonal antibodies. Acta Neuropathol. 1993;85(6):611–616. [PubMed]
  • Louis DN, von Deimling A, Chung RY, Rubio MP, Whaley JM, Eibl RH, Ohgaki H, Wiestler OD, Thor AD, Seizinger BR. Comparative study of p53 gene and protein alterations in human astrocytic tumors. J Neuropathol Exp Neurol. 1993 Jan;52(1):31–38. [PubMed]
  • Chozick BS, Pezzullo JC, Epstein MH, Finch PW. Prognostic implications of p53 overexpression in supratentorial astrocytic tumors. Neurosurgery. 1994 Nov;35(5):831–838. [PubMed]
  • Lane DP. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. [PubMed]
  • Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992 Jun 26;69(7):1237–1245. [PubMed]
  • von Deimling A, von Ammon K, Schoenfeld D, Wiestler OD, Seizinger BR, Louis DN. Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol. 1993 Jan;3(1):19–26. [PubMed]
  • Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Jr, Butel JS, Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992 Mar 19;356(6366):215–221. [PubMed]
  • von Deimling A, Bender B, Jahnke R, Waha A, Kraus J, Albrecht S, Wellenreuther R, Fassbender F, Nagel J, Menon AG, et al. Loci associated with malignant progression in astrocytomas: a candidate on chromosome 19q. Cancer Res. 1994 Mar 15;54(6):1397–1401. [PubMed]

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