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Long-term survivors of glioblastoma multiforme: clinical and molecular characteristics

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Abstract

Long term survival is rare in patients with glioblastoma multiforme (GBM). To determine if the tumors of patients with long survivals constitute a subgroup of patients with identifiable molecular genetic characteristics, we studied the p53 gene and Epidermal Growth Factor Receptor (EGF-R) expression in long-term survivors of GBM. A review of the Tumor Registry of Memorial Hospital for Cancer and Allied Diseases documented that 521 patients were treated for GBM between 1954 and 1987 and that 12 patients had seven-year or longer survivals. Six additional long-term survivors were identified from other institutions. After pathological re-examination, the diagnosis of 8 of these 18 (44%) tumors was changed to other histologic tumor types. Using immunohistochemical analysis, 4 of 10 confirmed malignant gliomas had over-expression of p53. Polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis and sequence analysis of these 4 tumors showed no p53 mutations in exons 5–8, the region where most mutations have been reported in human malignancies. Immunohistochemical analysis for EGF-R was performed on the tumors of the 10 long-term survivors. EGF-R over-expression was identified in 4 (40%), which is consistent with previous reported studies for GBM in general. These findings suggest that there is a subset of GBM defined by the accumulation of wild-type p53 and that the over-expression of EGF-R does not preclude long-term survival. The seven-year survival rate for confirmed GBM in patients from the Memorial Hospital Tumor Registry was at least 1%.

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References

  1. Chandler K, Prados M, Malec M, Wilson C: Long-term survival in patients with glioblastoma multiforme. Neurosurgery 32: 716–720, 1993

    Google Scholar 

  2. Phuphanich S, Ferrall S, Greenberg H: Long-term survival in malignant glioma. J Fla Med Assoc 80: 181–184, 1993

    Google Scholar 

  3. Salford L, Brun A, Nirfalk S: Ten-year survival among patients with supratentorial astrocytomas grade III and IV. J Neurosurg 69: 506–509, 1988

    Google Scholar 

  4. Vertosick F, Selker R: Long-term survival after the diagnosis of malignant glioma: a series of 22 patients surviving more than 4 years after diagnosis. Surg Neurol 38: 359–363, 1992

    Google Scholar 

  5. Lang FF, Miller DC, Koslow M, Newcomb EW: Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg 81: 427–436, 1994

    Google Scholar 

  6. Louis DN, Rubio M-P, Correa BS, Gusella JF, Von Deimling A: Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens. J Neuropathol Exp Neurol 52: 507–515, 1993

    Google Scholar 

  7. Kyritsis AP, Saya H: Epidemiology, cytogenetics, and molecular biology of brain tumors. Curr Opin Oncol 5: 474–480, 1993

    Google Scholar 

  8. Louis DN: The p53 gene and protein in human brain tumors. J Neuropathol Exp Neurol 53: 11–21, 1994

    Google Scholar 

  9. Hollstein M, Sidranksy D, Vogelstein B, Harris CC: p53 mutations in human cancers. Science 253: 49–53, 1991

    Google Scholar 

  10. Finlay CA, Hinds PW Tan T-H, Eliyahu D, Oren M, Levine AJ: Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol 8: 531–539, 1988

    Google Scholar 

  11. Finlay CA, Hinds PW, Levine AJ: The p53 proto-oncogene can act as a suppressor of transformation. Cell 57: 1083–1093, 1982

    Google Scholar 

  12. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Bayin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B: Mutations in the p53 gene occur in diverse tumor types. Nature 342: 705–708, 1989

    Google Scholar 

  13. von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, Kleihaus P, Chung RY, Wiestler OD, Seizinger BR: p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52: 2987–2990, 1992

    Google Scholar 

  14. Jaros E, Perry R, Adam L, Kelly PJ, Crawford PJ, Kalbag RM, Mendelow AD, Sengupta RP, Pearson ADJ: Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumors. Br J Cancer 66: 373–385, 1992

    Google Scholar 

  15. Wong AJ, Bigner SH, Bigner DS: Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84: 6899–6903, 1987

    Google Scholar 

  16. Agosti R, Leuthold M, Gullick W, Yasargil M, Wiestler O: Expression of the epidermal growth factor receptor in astrocytic tumors is specifically associated with glioblastoma multiforme. Virchows Archiv 420: 321–325, 1992

    Google Scholar 

  17. von Deimling A, Louis DN, von Ammon K, Petersen I, Hoell T, Chung RY, Martuza R, Schoenfeld D, Yasargil MG, Wiestler OD, Seizinger BR: Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J Neurosurg 77: 295–301, 1992

    Google Scholar 

  18. Wong AJ, Ruppert JM, Bigner SH, Grzeschik CH, Humphrey PA, Bigner DS, Vogelstein B: Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci USA 89: 2965–2969, 1992

    Google Scholar 

  19. Nicholson S, Sainsbury JRC, Halcrow P, Chambers P, Farndon JR, Harris AL: Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer. Lancet 1: 182–185, 1989

    Google Scholar 

  20. Hurtt MR, Moossy J, Donovan-Peluso M, Locker J: Amplification of epidermal growth factor receptor gene in gliomas: histopathology and prognosis. J Neuropathol Exp Neurol 51: 84–90, 1992

    Google Scholar 

  21. Torp S, Helseth E, Dalen A, Unsgaard G: Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas. Acta Neurochir (Wien) 117: 182–186, 1992

    Google Scholar 

  22. Burger PC, Green SB: Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59: 1617–1625, 1987

    Google Scholar 

  23. Netsky M, August B, Fowler W: The longevity of patients with glioblastoma multiforme. J Neurosurg 7: 261–269, 1950

    Google Scholar 

  24. Schlegel U, Rosenfeld MR, Volkenandt M, Rosenblum M, Dalmau J, Furneaux H: p53 gene mutations in primary lung tumors are conserved in brain metastases. J Neurooncol 14: 93–100, 1992

    Google Scholar 

  25. Sanger F, Nicklen S, Coulson A: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977

    Google Scholar 

  26. Ullén H, Mattson B, Collins V: Long-term survival after malignant glioma. Acta Oncol 29: 875–878, 1990

    Google Scholar 

  27. Kawano N: Pleomorphic xanthoastrocytoma: some new observations. Clin Neuropathol 11: 323–328, 1992

    Google Scholar 

  28. Kepes JJ: Pleomorphic xanthoastrocytoma: the birth of a diagnosis and a concept. Brain Pathol 3: 269–274, 1993

    Google Scholar 

  29. Thomas C, Golden B: Pleomorphic xanthoastrocytoma: report of two cases and brief review of the literature. Clin Neuropathol 12: 97–101, 1993

    Google Scholar 

  30. Frankel RH, Bayona W, Koslow M, Newcomb EW: p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res 52: 1427–1433, 1992

    Google Scholar 

  31. Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum M, Cavanee W, Vogelstein B: Clonal expansion of p53 mutant cells is associated with brain tumor progression. Nature 355: 846–847, 1992

    Google Scholar 

  32. Pardo FS, Hsu DW, Hedley-Whyte ET, Efird J, Schmidt EV: High p53 expression is prognostic of overall survival in adult supratentorial astrocytoma patients. J Neuro-Oncol 15(Suppl): S19, 1993

    Google Scholar 

  33. Rasheed BKA, McLendon RE, Herndon JE, Friedman HS, Friedman AH Bigner DD, Bigner SH: Alterations of the TP53 gene in human gliomas. Cancer Res 54: 1324–1330, 1994

    Google Scholar 

  34. Iggo R, Gatter K, Bartek J, Lane D, Harris AL: Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335: 675–679, 1990

    Google Scholar 

  35. Lang FF, Miller DC, Pisharody S, Koslow M, Newcomb EW: High frequency of p53 protein accumulation without p53 gene mutation in human juvenile pilocytic, low grade and anaplastic astrocytomas. Oncogene 9: 949–954, 1994

    Google Scholar 

  36. Rubio M-P, von Deimling A, Yandell D, Wiestler O, Gusella J, Louis D: Accumulation of wild-type p53 protein in human astrocytomas. Cancer Res 53: 3465–3467, 1993

    Google Scholar 

  37. Isola J, Visakorpi T, Holli K, Kallioniemi O: Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst 84: 1109–1114, 1992

    Google Scholar 

  38. Esrig D, Spruck CH, Nichols PW Chaiwun B, Steven K, Groshen S, Chen S-C, Skinner DG, Jones PA, Cote RJ: p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer. Am J Pathol 143: 1389–1397, 1993

    Google Scholar 

  39. 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 53: 2736–2739, 1993

    Google Scholar 

  40. McIlwrath AJ, Vasey PA, Ross GM, Brown R: Cell cycle arrests and radiosensitivity of human tumor cell lines: dependence on wild-type p53 for radiosensitivity. Cancer Res 54: 3718–3722, 1994

    Google Scholar 

  41. Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, Housman DE, Jacks T p53 status and the efficacy of cancer therapy in vivo. Science 266: 807–810, 1994

    Google Scholar 

  42. Dorward NL, Hawkins RA, Whittle IR: Epidermal growth factor receptor activity and clinical outcome in glioblastoma and meningioma. Br J Neurosurg 7: 197–199, 1993

    Google Scholar 

  43. Pigott TJ, Robson DK, Palmer J, Ward LM: Expression of epidermal growth factor receptor in human glioblastoma multiforme. Br J Neurosurg 7: 261–265, 1993

    Google Scholar 

  44. Hiesiger EM, Hayes RL, Pierz DM, Budzilovich GN: Prognostic relevance of epidermal growth factor receptor (EGF-R) and c-neu/erbB2 expression in glioblastomas (GBMs). J Neuro-oncol 16: 93–104, 1993

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, California

    Michon Morita

  2. Department of Pathology (Neuropathology), Memorial Sloan-Kettering Cancer Center, New York, New York

    Marc K. Rosenblum

  3. Division of Neurosurgery, Department of Surgery, Cornell University Medical College, New York, New York

    Mark H. Bilsky & Richard A.R. Fraser

  4. Department of Neurology and the Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Myrna R. Rosenfeld

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  1. Michon Morita
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  4. Richard A.R. Fraser
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  5. Myrna R. Rosenfeld
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Morita, M., Rosenblum, M.K., Bilsky, M.H. et al. Long-term survivors of glioblastoma multiforme: clinical and molecular characteristics. J Neuro-Oncol 27, 259–266 (1996). https://doi.org/10.1007/BF00165483

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