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. 1999 Feb;79(5-6):927–932. doi: 10.1038/sj.bjc.6690148

Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study

P Lenner 1, F Wiklund 1, S O Emdin 1, C Arnerlöv 2, C Eklund 3, G Hallmans 4, H Zentgraf 5, J Dillner 3
PMCID: PMC2362685  PMID: 10070892

Abstract

To perform an epidemiological evaluation of the predictive value of p53 autoantibodies in breast cancer, we measured antibodies against p53 in serum samples from 165 breast cancer patients in comparison with serum samples from 330 healthy controls, selected from the same population as the cases and matched for age, sex and specimen storage time. Median age of patients was 51 years (range 25–64 years). Presence of serum p53 autoantibodies was analysed by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting. The lower ELISA reactivities were similar for cases and controls, but presence of high-level reactivity was more common among cases than among controls [odds ratio (OR) 9.03, 95% confidence interval (CI) 2.40–50.43]. Presence of Western blot-detected p53 autoantibodies had a very similar association (OR 10.8, CI 3.0–59.4). Among the cases, we also studied whether there was any correlation between level of anti-p53 antibodies and stage of the disease or survival. There was no significant correlation between presence of antibodies and stage of the disease. There was a significant negative correlation between presence of p53 antibodies and survival (P= 0.003). A stepwise multivariate Cox regression analysis showed that T-stage, age and presence of anti-p53 antibodies were significant independent prognostic variables, with a dose-dependent negative effect on survival for all three variables. We conclude that presence of anti-p53 antibodies are of significance both for the risk of having breast cancer and the risk of dying from breast cancer. 1999 Cancer Research Campaign

Keywords: breast cancer, p53, antibodies, case–control study, survival

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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. Barnes D. M., Dublin E. A., Fisher C. J., Levison D. A., Millis R. R. Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis? Hum Pathol. 1993 May;24(5):469–476. doi: 10.1016/0046-8177(93)90158-d. [DOI] [PubMed] [Google Scholar]
  3. Coomber D., Hawkins N. J., Clark M., Meagher A., Ward R. L. Characterisation and clinicopathological correlates of serum anti-p53 antibodies in breast and colon cancer. J Cancer Res Clin Oncol. 1996;122(12):757–762. doi: 10.1007/BF01209124. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Davidoff A. M., Humphrey P. A., Iglehart J. D., Marks J. R. Genetic basis for p53 overexpression in human breast cancer. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5006–5010. doi: 10.1073/pnas.88.11.5006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Davidoff A. M., Kerns B. J., Iglehart J. D., Marks J. R. Maintenance of p53 alterations throughout breast cancer progression. Cancer Res. 1991 May 15;51(10):2605–2610. [PubMed] [Google Scholar]
  8. Green J. A., Mudenda B., Jenkins J., Leinster S. J., Tarunina M., Green B., Robertson L. Serum p53 auto-antibodies: incidence in familial breast cancer. Eur J Cancer. 1994;30A(5):580–584. doi: 10.1016/0959-8049(94)90523-1. [DOI] [PubMed] [Google Scholar]
  9. Hanzal E., Gitsch G., Kohlberger P., Dadak C., Miechowiecka N., Breitenecker G. Immunohistochemical detection of mutant p53-suppressor gene product in patients with breast cancer: influence on metastasis-free survival. Anticancer Res. 1992 Nov-Dec;12(6B):2325–2329. [PubMed] [Google Scholar]
  10. Houbiers J. G., van der Burg S. H., van de Watering L. M., Tollenaar R. A., Brand A., van de Velde C. J., Melief C. J. Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Cancer. 1995 Sep;72(3):637–641. doi: 10.1038/bjc.1995.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Isola J., Visakorpi T., Holli K., Kallioniemi O. P. 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. 1992 Jul 15;84(14):1109–1114. doi: 10.1093/jnci/84.14.1109. [DOI] [PubMed] [Google Scholar]
  12. Labrecque S., Naor N., Thomson D., Matlashewski G. Analysis of the anti-p53 antibody response in cancer patients. Cancer Res. 1993 Aug 1;53(15):3468–3471. [PubMed] [Google Scholar]
  13. Lubin R., Schlichtholz B., Teillaud J. L., Garay E., Bussel A., Wild C. P. p53 antibodies in patients with various types of cancer: assay, identification, and characterization. Clin Cancer Res. 1995 Dec;1(12):1463–1469. [PubMed] [Google Scholar]
  14. Mudenda B., Green J. A., Green B., Jenkins J. R., Robertson L., Tarunina M., Leinster S. J. The relationship between serum p53 autoantibodies and characteristics of human breast cancer. Br J Cancer. 1994 Jun;69(6):1115–1119. doi: 10.1038/bjc.1994.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Osborne R. J., Merlo G. R., Mitsudomi T., Venesio T., Liscia D. S., Cappa A. P., Chiba I., Takahashi T., Nau M. M., Callahan R. Mutations in the p53 gene in primary human breast cancers. Cancer Res. 1991 Nov 15;51(22):6194–6198. [PubMed] [Google Scholar]
  16. Ostrowski J. L., Sawan A., Henry L., Wright C., Henry J. A., Hennessy C., Lennard T. J., Angus B., Horne C. H. p53 expression in human breast cancer related to survival and prognostic factors: an immunohistochemical study. J Pathol. 1991 May;164(1):75–81. doi: 10.1002/path.1711640113. [DOI] [PubMed] [Google Scholar]
  17. Peyrat J. P., Bonneterre J., Lubin R., Vanlemmens L., Fournier J., Soussi T. Prognostic significance of circulating P53 antibodies in patients undergoing surgery for locoregional breast cancer. Lancet. 1995 Mar 11;345(8950):621–622. doi: 10.1016/s0140-6736(95)90523-5. [DOI] [PubMed] [Google Scholar]
  18. Regidor P. A., Regidor M., Callies R., Schindler A. E. Detection of p53 auto-antibodies in the sera of breast cancer patients with a new recurrence using an ELISA assay. Does a correlation with the recurrence free interval exist? Eur J Gynaecol Oncol. 1996;17(3):192–199. [PubMed] [Google Scholar]
  19. Ryder S. D., Rizzi P. M., Volkmann M., Metivier E., Pereira L. M., Galle P. R., Naoumov N. V., Zentgraf H., Williams R. Use of specific ELISA for the detection of antibodies directed against p53 protein in patients with hepatocellular carcinoma. J Clin Pathol. 1996 Apr;49(4):295–299. doi: 10.1136/jcp.49.4.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schlichtholz B., Legros Y., Gillet D., Gaillard C., Marty M., Lane D., Calvo F., Soussi T. The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res. 1992 Nov 15;52(22):6380–6384. [PubMed] [Google Scholar]
  21. Silvestrini R., Benini E., Daidone M. G., Veneroni S., Boracchi P., Cappelletti V., Di Fronzo G., Veronesi U. p53 as an independent prognostic marker in lymph node-negative breast cancer patients. J Natl Cancer Inst. 1993 Jun 16;85(12):965–970. doi: 10.1093/jnci/85.12.965. [DOI] [PubMed] [Google Scholar]
  22. Stenmark-Askmalm M., Stål O., Sullivan S., Ferraud L., Sun X. F., Carstensen J., Nordenskjöld B. Cellular accumulation of p53 protein: an independent prognostic factor in stage II breast cancer. Eur J Cancer. 1994;30A(2):175–180. doi: 10.1016/0959-8049(94)90082-5. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Vojtesek B., Kovarik J., Dolezalova H., Nenutil R., Havlis P., Brentani R. R., Lane D. P. Absence of p53 autoantibodies in a significant proportion of breast cancer patients. Br J Cancer. 1995 Jun;71(6):1253–1256. doi: 10.1038/bjc.1995.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Willsher P. C., Pinder S. E., Robertson L., Nicholson R. I., Ellis I. O., Bell J. A., Blamey R. W., Green J. A., Robertson J. F. The significance of p53 autoantibodies in the serum of patients with breast cancer. Anticancer Res. 1996 Mar-Apr;16(2):927–930. [PubMed] [Google Scholar]
  26. 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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