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British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Jun;71(6):1253–1256. doi: 10.1038/bjc.1995.242

Absence of p53 autoantibodies in a significant proportion of breast cancer patients.

B Vojtesek 1, J Kovarik 1, H Dolezalova 1, R Nenutil 1, P Havlis 1, R R Brentani 1, D P Lane 1
PMCID: PMC2033849  PMID: 7779720

Abstract

We analysed antibodies specific for human p53 in sera from primary breast cancer patients using three different immunoassays and we related these results to the p53 level in tumour tissue detected by immunohistochemistry. Only 44% (11/25) of apparently enzyme-linked immunosorbent assay (ELISA)-positive sera were from patients with a high level of p53 protein in more than 50% of their tumour cells. Surprisingly, 36% (9/25) of the sera originated from patients with no detectable p53 protein at all. Immunoprecipitation data suggested that the reason for this discrepancy is that at least some of the antibodies detected as positive in the ELISA in these sera from patients with clinical stage I and stage II breast cancers may be induced by immunogens other than p53 protein. Many of these reactions give apparently positive signals in a variety of p53 assays, and very stringent analysis is required to avoid possible misinterpretation of these responses as a p53-specific B-cell response in human cancer patients.

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Selected References

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  1. Allred D. C., Clark G. M., Elledge R., Fuqua S. A., Brown R. W., Chamness G. C., Osborne C. K., McGuire W. L. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst. 1993 Feb 3;85(3):200–206. doi: 10.1093/jnci/85.3.200. [DOI] [PubMed] [Google Scholar]
  2. Caron de Fromentel C., May-Levin F., Mouriesse H., Lemerle J., Chandrasekaran K., May P. Presence of circulating antibodies against cellular protein p53 in a notable proportion of children with B-cell lymphoma. Int J Cancer. 1987 Feb 15;39(2):185–189. doi: 10.1002/ijc.2910390211. [DOI] [PubMed] [Google Scholar]
  3. Crawford L. V., Pim D. C., Bulbrook R. D. Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer. 1982 Oct 15;30(4):403–408. doi: 10.1002/ijc.2910300404. [DOI] [PubMed] [Google Scholar]
  4. Davidoff A. M., Iglehart J. D., Marks J. R. Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3439–3442. doi: 10.1073/pnas.89.8.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gannon J. V., Greaves R., Iggo R., Lane D. P. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hassapoglidou S., Diamandis E. P. Antibodies to the p53 tumor suppressor gene product quantified in cancer patient serum with a time-resolved immunofluorometric technique. Clin Biochem. 1992 Dec;25(6):445–449. doi: 10.1016/0009-9120(92)90090-f. [DOI] [PubMed] [Google Scholar]
  7. Hupp T. R., Meek D. W., Midgley C. A., Lane D. P. Regulation of the specific DNA binding function of p53. Cell. 1992 Nov 27;71(5):875–886. doi: 10.1016/0092-8674(92)90562-q. [DOI] [PubMed] [Google Scholar]
  8. Lubin R., Schlichtholz B., Bengoufa D., Zalcman G., Trédaniel J., Hirsch A., Caron de Fromentel C., Preudhomme C., Fenaux P., Fournier G. Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53: distribution on primary structure and exposure on protein surface. Cancer Res. 1993 Dec 15;53(24):5872–5876. [PubMed] [Google Scholar]
  9. Midgley C. A., Fisher C. J., Bártek J., Vojtesek B., Lane D., Barnes D. M. Analysis of p53 expression in human tumours: an antibody raised against human p53 expressed in Escherichia coli. J Cell Sci. 1992 Jan;101(Pt 1):183–189. doi: 10.1242/jcs.101.1.183. [DOI] [PubMed] [Google Scholar]
  10. Schlichtholz B., Trédaniel J., Lubin R., Zalcman G., Hirsch A., Soussi T. Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein. Br J Cancer. 1994 May;69(5):809–816. doi: 10.1038/bjc.1994.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Thor A. D., Moore DH I. I., Edgerton S. M., Kawasaki E. S., Reihsaus E., Lynch H. T., Marcus J. N., Schwartz L., Chen L. C., Mayall B. H. Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst. 1992 Jun 3;84(11):845–855. doi: 10.1093/jnci/84.11.845. [DOI] [PubMed] [Google Scholar]
  12. Vojtesek B., Bártek J., Midgley C. A., Lane D. P. An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods. 1992 Jul 6;151(1-2):237–244. doi: 10.1016/0022-1759(92)90122-a. [DOI] [PubMed] [Google Scholar]
  13. Vojtesek B., Fisher C. J., Barnes D. M., Lane D. P. Comparison between p53 staining in tissue sections and p53 proteins levels measured by an ELISA technique. Br J Cancer. 1993 Jun;67(6):1254–1258. doi: 10.1038/bjc.1993.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Winter S. F., Minna J. D., Johnson B. E., Takahashi T., Gazdar A. F., Carbone D. P. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res. 1992 Aug 1;52(15):4168–4174. [PubMed] [Google Scholar]

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