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British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(3-4):604–610. doi: 10.1038/sj.bjc.6690095

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

R Saffroy 1, J-C Lelong 2, D Azoulay 3, M Salvucci 1, M Reynes 4, H Bismuth 3, B Debuire 1, A Lemoine 1
PMCID: PMC2362420  PMID: 10027337

Abstract

p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12–30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alpha-fetoprotein levels and clinicopathological characterics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P < 0.03 and P < 0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative ‘good prognosis’ in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis. © 1999 Cancer Research Campaign

Keywords: hepatocellular carcinoma, p53 antibodies, liver surgery

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Selected References

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  1. Akashi Y., Koreeda C., Enomoto S., Uchiyama S., Mizuno T., Shiozaki Y., Sameshima Y., Inoue K. Prognosis of unresectable hepatocellular carcinoma: an evaluation based on multivariate analysis of 90 cases. Hepatology. 1991 Aug;14(2):262–268. [PubMed] [Google Scholar]
  2. Angelopoulou K., Diamandis E. P., Sutherland D. J., Kellen J. A., Bunting P. S. Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers. Int J Cancer. 1994 Aug 15;58(4):480–487. doi: 10.1002/ijc.2910580404. [DOI] [PubMed] [Google Scholar]
  3. Angelopoulou K., Rosen B., Stratis M., Yu H., Solomou M., Diamandis E. P. Circulating antibodies against p53 protein in patients with ovarian carcinoma. Correlation with clinicopathologic features and survival. Cancer. 1996 Nov 15;78(10):2146–2152. [PubMed] [Google Scholar]
  4. Bismuth H., Chiche L., Adam R., Castaing D., Diamond T., Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg. 1993 Aug;218(2):145–151. doi: 10.1097/00000658-199308000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bismuth H., Morino M., Sherlock D., Castaing D., Miglietta C., Cauquil P., Roche A. Primary treatment of hepatocellular carcinoma by arterial chemoembolization. Am J Surg. 1992 Apr;163(4):387–394. doi: 10.1016/0002-9610(92)90039-t. [DOI] [PubMed] [Google Scholar]
  6. Bourhis J., Lubin R., Roche B., Koscielny S., Bosq J., Dubois I., Talbot M., Marandas P., Schwaab G., Wibault P. Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma. J Natl Cancer Inst. 1996 Sep 4;88(17):1228–1233. doi: 10.1093/jnci/88.17.1228. [DOI] [PubMed] [Google Scholar]
  7. Challen C., Lunec J., Warren W., Collier J., Bassendine M. F. Analysis of the p53 tumor-suppressor gene in hepatocellular carcinomas from Britain. Hepatology. 1992 Dec;16(6):1362–1366. doi: 10.1002/hep.1840160610. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. D'Errico A., Grigioni W. F., Fiorentino M., Baccarini P., Grazi G. L., Mancini A. M. Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma: an immunohistochemical study on 109 Italian patients. Pathol Int. 1994 Sep;44(9):682–687. doi: 10.1111/j.1440-1827.1994.tb02947.x. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Debuire B., Paterlini P., Pontisso P., Basso G., May E. Analysis of the p53 gene in European hepatocellular carcinomas and hepatoblastomas. Oncogene. 1993 Aug;8(8):2303–2306. [PubMed] [Google Scholar]
  12. Ganne-Carrié N., Chastang C., Chapel F., Munz C., Pateron D., Sibony M., Dény P., Trinchet J. C., Callard P., Guettier C. Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis. Hepatology. 1996 May;23(5):1112–1118. doi: 10.1002/hep.510230527. [DOI] [PubMed] [Google Scholar]
  13. Gansauge S., Gansauge F., Negri G., Galle P., Müller J., Nüssler A. K., Poch B., Beger H. G. The role of anti-p53-autoantibodies in pancreatic disorders. Int J Pancreatol. 1996 Jun;19(3):171–178. doi: 10.1007/BF02787365. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Kaur J., Srivastava A., Ralhan R. Serum p53 antibodies in patients with oral lesions: correlation with p53/HSP70 complexes. Int J Cancer. 1997 Dec 19;74(6):609–613. doi: 10.1002/(sici)1097-0215(19971219)74:6<609::aid-ijc9>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  16. Lechner M. S., Laimins L. A. Inhibition of p53 DNA binding by human papillomavirus E6 proteins. J Virol. 1994 Jul;68(7):4262–4273. doi: 10.1128/jvi.68.7.4262-4273.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lubin R., Zalcman G., Bouchet L., Trédanel J., Legros Y., Cazals D., Hirsch A., Soussi T. Serum p53 antibodies as early markers of lung cancer. Nat Med. 1995 Jul;1(7):701–702. doi: 10.1038/nm0795-701. [DOI] [PubMed] [Google Scholar]
  18. O'Reilly D. R., Miller L. K. Expression and complex formation of simian virus 40 large T antigen and mouse p53 in insect cells. J Virol. 1988 Sep;62(9):3109–3119. doi: 10.1128/jvi.62.9.3109-3119.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Shiota G., Kishimoto Y., Suyama A., Okubo M., Katayama S., Harada K., Ishida M., Hori K., Suou T., Kawasaki H. Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma. J Hepatol. 1997 Oct;27(4):661–668. doi: 10.1016/s0168-8278(97)80083-9. [DOI] [PubMed] [Google Scholar]
  21. Trivers G. E., Cawley H. L., DeBenedetti V. M., Hollstein M., Marion M. J., Bennett W. P., Hoover M. L., Prives C. C., Tamburro C. C., Harris C. C. Anti-p53 antibodies in sera of workers occupationally exposed to vinyl chloride. J Natl Cancer Inst. 1995 Sep 20;87(18):1400–1407. doi: 10.1093/jnci/87.18.1400. [DOI] [PubMed] [Google Scholar]
  22. Trivers G. E., De Benedetti V. M., Cawley H. L., Caron G., Harrington A. M., Bennett W. P., Jett J. R., Colby T. V., Tazelaar H., Pairolero P. Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer. Clin Cancer Res. 1996 Oct;2(10):1767–1775. [PubMed] [Google Scholar]
  23. Volkmann M., Müller M., Hofmann W. J., Meyer M., Hagelstein J., Räth U., Kommerell B., Zentgraf H., Galle P. R. The humoral immune response to p53 in patients with hepatocellular carcinoma is specific for malignancy and independent of the alpha-fetoprotein status. Hepatology. 1993 Sep;18(3):559–565. [PubMed] [Google Scholar]
  24. Wollenberg B., Jan N. V., Pitzke P., Reiter W., Stieber P. Anti-p53 antibodies in serum of smokers and head and neck cancer patients. Anticancer Res. 1997 Jan-Feb;17(1A):413–418. [PubMed] [Google Scholar]
  25. Yamashita Y., Takahashi M., Koga Y., Saito R., Nanakawa S., Hatanaka Y., Sato N., Nakashima K., Urata J., Yoshizumi K. Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion. Cancer. 1991 Jan 15;67(2):385–391. doi: 10.1002/1097-0142(19910115)67:2<385::aid-cncr2820670212>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]

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