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Br J Cancer. Aug 1992; 66(2): 373–385.
PMCID: PMC1977794

Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours.

Abstract

The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival.

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  • Arita N, Hayakawa T, Izumoto S, Taki T, Ohnishi T, Yamamoto H, Bitoh S, Mogami H. Epidermal growth factor receptor in human glioma. J Neurosurg. 1989 Jun;70(6):916–919. [PubMed]
  • Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. [PubMed]
  • Banks L, Matlashewski G, Crawford L. Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem. 1986 Sep 15;159(3):529–534. [PubMed]
  • Bigner SH, Mark J, Friedman HS, Biegel JA, Bigner DD. Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet Cytogenet. 1988 Jan;30(1):91–101. [PubMed]
  • Bigner SH, Mark J, Mahaley MS, Bigner DD. Patterns of the early, gross chromosomal changes in malignant human gliomas. Hereditas. 1984;101(1):103–113. [PubMed]
  • Bigner SH, Vogelstein B. Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma. Brain Pathol. 1990 Sep;1(1):12–18. [PubMed]
  • Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 1991 Apr 4;350(6317):429–431. [PubMed]
  • Brown DC, Gatter KC. Monoclonal antibody Ki-67: its use in histopathology. Histopathology. 1990 Dec;17(6):489–503. [PubMed]
  • Carpenter G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem. 1987;56:881–914. [PubMed]
  • Cattoretti G, Rilke F, Andreola S, D'Amato L, Delia D. P53 expression in breast cancer. Int J Cancer. 1988 Feb 15;41(2):178–183. [PubMed]
  • Dippold WG, Jay G, DeLeo AB, Khoury G, Old LJ. p53 transformation-related protein: detection by monoclonal antibody in mouse and human cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1695–1699. [PMC free article] [PubMed]
  • el-Azouzi M, Chung RY, Farmer GE, Martuza RL, Black PM, Rouleau GA, Hettlich C, Hedley-Whyte ET, Zervas NT, Panagopoulos K, et al. Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7186–7190. [PMC free article] [PubMed]
  • Finlay CA, Hinds PW, Levine AJ. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. [PubMed]
  • Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984 Oct;133(4):1710–1715. [PubMed]
  • Griffin CA, Hawkins AL, Packer RJ, Rorke LB, Emanuel BS. Chromosome abnormalities in pediatric brain tumors. Cancer Res. 1988 Jan 1;48(1):175–180. [PubMed]
  • Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991 Apr 4;350(6317):427–428. [PubMed]
  • Humphrey PA, Wong AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE, Friedman HS, Kwatra MM, Bigner SH, Bigner DD. Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4207–4211. [PMC free article] [PubMed]
  • Hunter T. The epidermal growth factor receptor gene and its product. Nature. 1984 Oct 4;311(5985):414–416. [PubMed]
  • Iggo R, Gatter K, Bartek J, Lane D, Harris AL. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990 Mar 24;335(8691):675–679. [PubMed]
  • James CD, Carlbom E, Dumanski JP, Hansen M, Nordenskjold M, Collins VP, Cavenee WK. Clonal genomic alterations in glioma malignancy stages. Cancer Res. 1988 Oct 1;48(19):5546–5551. [PubMed]
  • James CD, Carlbom E, Nordenskjold M, Collins VP, Cavenee WK. Mitotic recombination of chromosome 17 in astrocytomas. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2858–2862. [PMC free article] [PubMed]
  • Levine AJ, Momand J. Tumor suppressor genes: the p53 and retinoblastoma sensitivity genes and gene products. Biochim Biophys Acta. 1990 Jun 1;1032(1):119–136. [PubMed]
  • Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985 Jan 10;313(5998):144–147. [PubMed]
  • Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 1984 Feb;44(2):753–760. [PubMed]
  • Malkin D, Li FP, Strong LC, Fraumeni JF, Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233–1238. [PubMed]
  • Masuda H, Miller C, Koeffler HP, Battifora H, Cline MJ. Rearrangement of the p53 gene in human osteogenic sarcomas. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7716–7719. [PMC free article] [PubMed]
  • Menon AG, Anderson KM, Riccardi VM, Chung RY, Whaley JM, Yandell DW, Farmer GE, Freiman RN, Lee JK, Li FP, et al. Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5435–5439. [PMC free article] [PubMed]
  • Mulligan LM, Matlashewski GJ, Scrable HJ, Cavenee WK. Mechanisms of p53 loss in human sarcomas. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5863–5867. [PMC free article] [PubMed]
  • Nistér M, Libermann TA, Betsholtz C, Pettersson M, Claesson-Welsh L, Heldin CH, Schlessinger J, Westermark B. Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-alpha and their receptors in human malignant glioma cell lines. Cancer Res. 1988 Jul 15;48(14):3910–3918. [PubMed]
  • Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. [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]
  • Reifenberger G, Prior R, Deckert M, Wechsler W. Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system. Virchows Arch A Pathol Anat Histopathol. 1989;414(2):147–155. [PubMed]
  • Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, Lane DP. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555–7559. [PMC free article] [PubMed]
  • Rorke LB, Gilles FH, Davis RL, Becker LE. Revision of the World Health Organization classification of brain tumors for childhood brain tumors. Cancer. 1985 Oct 1;56(7 Suppl):1869–1886. [PubMed]
  • Shapiro JR. Biology of gliomas: heterogeneity, oncogenes, growth factors. Semin Oncol. 1986 Mar;13(1):4–15. [PubMed]
  • Shaulsky G, Goldfinger N, Ben-Ze'ev A, Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol. 1990 Dec;10(12):6565–6577. [PMC free article] [PubMed]
  • Stanbridge EJ. Human tumor suppressor genes. Annu Rev Genet. 1990;24:615–657. [PubMed]
  • Stoscheck CM, King LE., Jr Functional and structural characteristics of EGF and its receptor and their relationship to transforming proteins. J Cell Biochem. 1986;31(2):135–152. [PubMed]
  • Stürzbecher HW, Addison C, Jenkins JR. Characterization of mutant p53-hsp72/73 protein-protein complexes by transient expression in monkey COS cells. Mol Cell Biol. 1988 Sep;8(9):3740–3747. [PMC free article] [PubMed]
  • Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602–8606. [PMC free article] [PubMed]
  • Thomas GA, Raffel C. Loss of heterozygosity on 6q, 16q, and 17p in human central nervous system primitive neuroectodermal tumors. Cancer Res. 1991 Jan 15;51(2):639–643. [PubMed]
  • Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B. Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6899–6903. [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]

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