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British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Mar;71(3):473–477. doi: 10.1038/bjc.1995.96

Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma.

R J Gilbertson 1, A D Pearson 1, R H Perry 1, E Jaros 1, P J Kelly 1
PMCID: PMC2033658  PMID: 7880726

Abstract

The expression and prognostic significance of the c-erbB-2 oncogene product was studied in 55 cases of childhood medulloblastoma. Forty-six of the 55 tumours (83.6%) expressed the c-erbB-2 product. The percentage of tumour cells expressing the c-erbB-2 product proved to be a significant indicator of patient outcome when analysed as both a categorical and a continuous variable. As a categorical variable, patients with more than 50% positive tumour cells had a significantly worse survival, with only 10% alive at 10 years vs 48% for those with less than 50% positive tumour cells (log rank P = 0.0049). To demonstrate that this observed prognostic significance was both independent and not a result of 'data-driven' categorisation, it was also entered into the Cox model as a continuous variable. Prognostic significance was retained in P = 0.038.

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Selected References

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  1. Allen J. C., Epstein F. Medulloblastoma and other primary malignant neuroectodermal tumors of the CNS. The effect of patients' age and extent of disease on prognosis. J Neurosurg. 1982 Oct;57(4):446–451. doi: 10.3171/jns.1982.57.4.0446. [DOI] [PubMed] [Google Scholar]
  2. Bargmann C. I., Weinberg R. A. Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5394–5398. doi: 10.1073/pnas.85.15.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berger M. S., Locher G. W., Saurer S., Gullick W. J., Waterfield M. D., Groner B., Hynes N. E. Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 1988 Mar 1;48(5):1238–1243. [PubMed] [Google Scholar]
  4. Berry M. P., Jenkin R. D., Keen C. W., Nair B. D., Simpson W. J. Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg. 1981 Jul;55(1):43–51. doi: 10.3171/jns.1981.55.1.0043. [DOI] [PubMed] [Google Scholar]
  5. Bigner S. H., Mark J., Friedman H. S., Biegel J. A., Bigner D. D. Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet Cytogenet. 1988 Jan;30(1):91–101. doi: 10.1016/0165-4608(88)90096-9. [DOI] [PubMed] [Google Scholar]
  6. Caputy A. J., McCullough D. C., Manz H. J., Patterson K., Hammock M. K. A review of the factors influencing the prognosis of medulloblastoma. The importance of cell differentiation. J Neurosurg. 1987 Jan;66(1):80–87. doi: 10.3171/jns.1987.66.1.0080. [DOI] [PubMed] [Google Scholar]
  7. Corbett I. P., Henry J. A., Angus B., Watchorn C. J., Wilkinson L., Hennessy C., Gullick W. J., Tuzi N. L., May F. E., Westley B. R. NCL-CB11, a new monoclonal antibody recognizing the internal domain of the c-erbB-2 oncogene protein effective for use on formalin-fixed, paraffin-embedded tissue. J Pathol. 1990 May;161(1):15–25. doi: 10.1002/path.1711610105. [DOI] [PubMed] [Google Scholar]
  8. Craft A. W., Amineddine H. A., Scott J. E., Wagget J. The Northern region Children's malignant disease registry 1968-82: incidence and survival. Br J Cancer. 1987 Dec;56(6):853–858. doi: 10.1038/bjc.1987.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Di Fiore P. P., Segatto O., Lonardo F., Fazioli F., Pierce J. H., Aaronson S. A. The carboxy-terminal domains of erbB-2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity. Mol Cell Biol. 1990 Jun;10(6):2749–2756. doi: 10.1128/mcb.10.6.2749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fukushige S., Matsubara K., Yoshida M., Sasaki M., Suzuki T., Semba K., Toyoshima K., Yamamoto T. Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol. 1986 Mar;6(3):955–958. doi: 10.1128/mcb.6.3.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Griffin C. A., Hawkins A. L., Packer R. J., Rorke L. B., Emanuel B. S. Chromosome abnormalities in pediatric brain tumors. Cancer Res. 1988 Jan 1;48(1):175–180. [PubMed] [Google Scholar]
  12. Gullick W. J., Berger M. S., Bennett P. L., Rothbard J. B., Waterfield M. D. Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer. 1987 Aug 15;40(2):246–254. doi: 10.1002/ijc.2910400221. [DOI] [PubMed] [Google Scholar]
  13. Gullick W. J., Love S. B., Wright C., Barnes D. M., Gusterson B., Harris A. L., Altman D. G. c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer. 1991 Mar;63(3):434–438. doi: 10.1038/bjc.1991.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gutman M., Ravia Y., Assaf D., Yamamoto T., Rozin R., Shiloh Y. Amplification of c-myc and c-erbB-2 proto-oncogenes in human solid tumors: frequency and clinical significance. Int J Cancer. 1989 Nov 15;44(5):802–805. doi: 10.1002/ijc.2910440509. [DOI] [PubMed] [Google Scholar]
  15. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  16. Hudziak R. M., Lewis G. D., Winget M., Fendly B. M., Shepard H. M., Ullrich A. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol Cell Biol. 1989 Mar;9(3):1165–1172. doi: 10.1128/mcb.9.3.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jenkin D., Goddard K., Armstrong D., Becker L., Berry M., Chan H., Doherty M., Greenberg M., Hendrick B., Hoffman H. Posterior fossa medulloblastoma in childhood: treatment results and a proposal for a new staging system. Int J Radiat Oncol Biol Phys. 1990 Aug;19(2):265–274. doi: 10.1016/0360-3016(90)90533-p. [DOI] [PubMed] [Google Scholar]
  18. Kameda T., Yasui W., Yoshida K., Tsujino T., Nakayama H., Ito M., Ito H., Tahara E. Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2 expression and the gene amplification. Cancer Res. 1990 Dec 15;50(24):8002–8009. [PubMed] [Google Scholar]
  19. Kokai Y., Cohen J. A., Drebin J. A., Greene M. I. Stage- and tissue-specific expression of the neu oncogene in rat development. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8498–8501. doi: 10.1073/pnas.84.23.8498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kopelson G., Linggood R. M., Kleinman G. M. Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management. Cancer. 1983 Jan 15;51(2):312–319. doi: 10.1002/1097-0142(19830115)51:2<312::aid-cncr2820510225>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  21. Lovekin C., Ellis I. O., Locker A., Robertson J. F., Bell J., Nicholson R., Gullick W. J., Elston C. W., Blamey R. W. c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer. 1991 Mar;63(3):439–443. doi: 10.1038/bjc.1991.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Natali P. G., Nicotra M. R., Bigotti A., Venturo I., Slamon D. J., Fendly B. M., Ullrich A. Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. Int J Cancer. 1990 Mar 15;45(3):457–461. doi: 10.1002/ijc.2910450314. [DOI] [PubMed] [Google Scholar]
  23. Peto R., Pike M. C. Conservatism of the approximation sigma (O-E)2-E in the logrank test for survival data or tumor incidence data. Biometrics. 1973 Sep;29(3):579–584. [PubMed] [Google Scholar]
  24. Poller D. N., Spendlove I., Baker C., Church R., Ellis I. O., Plowman G. D., Mayer R. J. Production and characterization of a polyclonal antibody to the c-erbB-3 protein: examination of c-erbB-3 protein expression in adenocarcinomas. J Pathol. 1992 Nov;168(3):275–280. doi: 10.1002/path.1711680306. [DOI] [PubMed] [Google Scholar]
  25. Quirke P., Pickles A., Tuzi N. L., Mohamdee O., Gullick W. J. Pattern of expression of c-erbB-2 oncoprotein in human fetuses. Br J Cancer. 1989 Jul;60(1):64–69. doi: 10.1038/bjc.1989.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schechter A. L., Stern D. F., Vaidyanathan L., Decker S. J., Drebin J. A., Greene M. I., Weinberg R. A. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984 Dec 6;312(5994):513–516. doi: 10.1038/312513a0. [DOI] [PubMed] [Google Scholar]
  27. Shalaby M. R., Shepard H. M., Presta L., Rodrigues M. L., Beverley P. C., Feldmann M., Carter P. Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene. J Exp Med. 1992 Jan 1;175(1):217–225. doi: 10.1084/jem.175.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
  29. Tagliabue E., Centis F., Campiglio M., Mastroianni A., Martignone S., Pellegrini R., Casalini P., Lanzi C., Ménard S., Colnaghi M. I. Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification. Int J Cancer. 1991 Apr 1;47(6):933–937. doi: 10.1002/ijc.2910470625. [DOI] [PubMed] [Google Scholar]
  30. Tait D. M., Thornton-Jones H., Bloom H. J., Lemerle J., Morris-Jones P. Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer. 1990 Apr;26(4):464–469. [PubMed] [Google Scholar]
  31. Winstanley J., Cooke T., Murray G. D., Platt-Higgins A., George W. D., Holt S., Myskov M., Spedding A., Barraclough B. R., Rudland P. S. The long term prognostic significance of c-erbB-2 in primary breast cancer. Br J Cancer. 1991 Mar;63(3):447–450. doi: 10.1038/bjc.1991.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yokota J., Yamamoto T., Toyoshima K., Terada M., Sugimura T., Battifora H., Cline M. J. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet. 1986 Apr 5;1(8484):765–767. doi: 10.1016/s0140-6736(86)91782-4. [DOI] [PubMed] [Google Scholar]
  33. Zerbini C., Gelber R. D., Weinberg D., Sallan S. E., Barnes P., Kupsky W., Scott R. M., Tarbell N. J. Prognostic factors in medulloblastoma, including DNA ploidy. J Clin Oncol. 1993 Apr;11(4):616–622. doi: 10.1200/JCO.1993.11.4.616. [DOI] [PubMed] [Google Scholar]

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