Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Jan 1;84(1):57–63. doi: 10.1054/bjoc.2000.1542

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

O Tominaga 1, K Unsal 1, G Zalcman 1,2, T Soussi 1
PMCID: PMC2363625  PMID: 11139314

Abstract

p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino- and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: p73 antibodies, p53 antibodies, tumour antigen, tumoral immune response

Full Text

The Full Text of this article is available as a PDF (293.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bessard A. C., Garay E., Lacronique V., Legros Y., Demarquay C., Houque A., Portefaix J. M., Granier C., Soussi T. Regulation of the specific DNA binding activity of Xenopus laevis p53: evidence for conserved regulation through the carboxy-terminus of the protein. Oncogene. 1998 Feb 19;16(7):883–890. doi: 10.1038/sj.onc.1201598. [DOI] [PubMed] [Google Scholar]
  2. Bártek J., Bártková J., Lukás J., Stasková Z., Vojtesek B., Lane D. P. Immunohistochemical analysis of the p53 oncoprotein on paraffin sections using a series of novel monoclonal antibodies. J Pathol. 1993 Jan;169(1):27–34. doi: 10.1002/path.1711690106. [DOI] [PubMed] [Google Scholar]
  3. Cai Y. C., Yang G. Y., Nie Y., Wang L. D., Zhao X., Song Y. L., Seril D. N., Liao J., Xing E. P., Yang C. S. Molecular alterations of p73 in human esophageal squamous cell carcinomas: loss of heterozygosity occurs frequently; loss of imprinting and elevation of p73 expression may be related to defective p53. Carcinogenesis. 2000 Apr;21(4):683–689. doi: 10.1093/carcin/21.4.683. [DOI] [PubMed] [Google Scholar]
  4. Chi S. G., Chang S. G., Lee S. J., Lee C. H., Kim J. I., Park J. H. Elevated and biallelic expression of p73 is associated withprogression of human bladder cancer. Cancer Res. 1999 Jun 15;59(12):2791–2793. [PubMed] [Google Scholar]
  5. 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]
  6. Hammel P., Boissier B., Chaumette M. T., Piedbois P., Rotman N., Kouyoumdjian J. C., Lubin R., Delchier J. C., Soussi T. Detection and monitoring of serum p53 antibodies in patients with colorectal cancer. Gut. 1997 Mar;40(3):356–361. doi: 10.1136/gut.40.3.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Herath N. I., Kew M. C., Whitehall V. L., Walsh M. D., Jass J. R., Khanna K. K., Young J., Powell L. W., Leggett B. A., Macdonald G. A. p73 is up-regulated in a subset of hepatocellular carcinomas. Hepatology. 2000 Mar;31(3):601–605. doi: 10.1002/hep.510310309. [DOI] [PubMed] [Google Scholar]
  8. Ikawa S., Nakagawara A., Ikawa Y. p53 family genes: structural comparison, expression and mutation. Cell Death Differ. 1999 Dec;6(12):1154–1161. doi: 10.1038/sj.cdd.4400631. [DOI] [PubMed] [Google Scholar]
  9. Kaghad M., Bonnet H., Yang A., Creancier L., Biscan J. C., Valent A., Minty A., Chalon P., Lelias J. M., Dumont X. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997 Aug 22;90(4):809–819. doi: 10.1016/s0092-8674(00)80540-1. [DOI] [PubMed] [Google Scholar]
  10. Kussie P. H., Gorina S., Marechal V., Elenbaas B., Moreau J., Levine A. J., Pavletich N. P. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. 1996 Nov 8;274(5289):948–953. doi: 10.1126/science.274.5289.948. [DOI] [PubMed] [Google Scholar]
  11. Lee L. A., Walsh P., Prater C. A., Su L. J., Marchbank A., Egbert T. B., Dellavalle R. P., Targoff I. N., Kaufman K. M., Chorzelski T. P. Characterization of an autoantigen associated with chronic ulcerative stomatitis: the CUSP autoantigen is a member of the p53 family. J Invest Dermatol. 1999 Aug;113(2):146–151. doi: 10.1046/j.1523-1747.1999.00651.x. [DOI] [PubMed] [Google Scholar]
  12. Legros Y., Lacabanne V., d'Agay M. F., Larsen C. J., Pla M., Soussi T. Production of human p53 specific monoclonal antibodies and their use in immunohistochemical studies of tumor cells. Bull Cancer. 1993 Feb;80(2):102–110. [PubMed] [Google Scholar]
  13. Legros Y., Lafon C., Soussi T. Linear antigenic sites defined by the B-cell response to human p53 are localized predominantly in the amino and carboxy-termini of the protein. Oncogene. 1994 Jul;9(7):2071–2076. [PubMed] [Google Scholar]
  14. Legros Y., Meyer A., Ory K., Soussi T. Mutations in p53 produce a common conformational effect that can be detected with a panel of monoclonal antibodies directed toward the central part of the p53 protein. Oncogene. 1994 Dec;9(12):3689–3694. [PubMed] [Google Scholar]
  15. Levine A. J. p53, the cellular gatekeeper for growth and division. Cell. 1997 Feb 7;88(3):323–331. doi: 10.1016/s0092-8674(00)81871-1. [DOI] [PubMed] [Google Scholar]
  16. Levrero M., De Laurenzi V., Costanzo A., Gong J., Wang J. Y., Melino G. The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci. 2000 May;113(Pt 10):1661–1670. doi: 10.1242/jcs.113.10.1661. [DOI] [PubMed] [Google Scholar]
  17. Loiseau H., Arsaut J., Demotes-Mainard J. p73 gene transcripts in human brain tumors: overexpression and altered splicing in ependymomas. Neurosci Lett. 1999 Mar 26;263(2-3):173–176. doi: 10.1016/s0304-3940(99)00130-5. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Marin M. C., Jost C. A., Irwin M. S., DeCaprio J. A., Caput D., Kaelin W. G., Jr Viral oncoproteins discriminate between p53 and the p53 homolog p73. Mol Cell Biol. 1998 Nov;18(11):6316–6324. doi: 10.1128/mcb.18.11.6316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marin M. C., Kaelin W. G., Jr p63 and p73: old members of a new family. Biochim Biophys Acta. 2000 May 17;1470(3):M93–M100. doi: 10.1016/s0304-419x(00)00010-x. [DOI] [PubMed] [Google Scholar]
  22. Ng S. W., Yiu G. K., Liu Y., Huang L. W., Palnati M., Jun S. H., Berkowitz R. S., Mok S. C. Analysis of p73 in human borderline and invasive ovarian tumor. Oncogene. 2000 Apr 6;19(15):1885–1890. doi: 10.1038/sj.onc.1203512. [DOI] [PubMed] [Google Scholar]
  23. Ory K., Legros Y., Auguin C., Soussi T. Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. EMBO J. 1994 Aug 1;13(15):3496–3504. doi: 10.1002/j.1460-2075.1994.tb06656.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Peters U. R., Tschan M. P., Kreuzer K. A., Baskaynak G., Lass U., Tobler A., Fey M. F., Schmidt C. A. Distinct expression patterns of the p53-homologue p73 in malignant and normal hematopoiesis assessed by a novel real-time reverse transcription-polymerase chain reaction assay and protein analysis. Cancer Res. 1999 Sep 1;59(17):4233–4236. [PubMed] [Google Scholar]
  25. Polge A., Bourgaux J. F., Bancel E., Pignodel C., Boyer J. C., Poirey S., de Bornier B. M., Balmes J. L., Bali J. P. p53 and follow-up of colorectal adenocarcinomas. Dig Dis Sci. 1998 Jul;43(7):1434–1442. doi: 10.1023/a:1018890126260. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Soussi T., Dehouche K., Béroud C. p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis. Hum Mutat. 2000;15(1):105–113. doi: 10.1002/(SICI)1098-1004(200001)15:1<105::AID-HUMU19>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  28. Soussi T. p53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000 Apr 1;60(7):1777–1788. [PubMed] [Google Scholar]
  29. Tannapfel A., Engeland K., Weinans L., Katalinic A., Hauss J., Mössner J., Wittekind C. Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver. Br J Cancer. 1999 Jun;80(7):1069–1074. doi: 10.1038/sj.bjc.6690465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tokuchi Y., Hashimoto T., Kobayashi Y., Hayashi M., Nishida K., Hayashi S., Imai K., Nakachi K., Ishikawa Y., Nakagawa K. The expression of p73 is increased in lung cancer, independent of p53 gene alteration. Br J Cancer. 1999 Jul;80(10):1623–1629. doi: 10.1038/sj.bjc.6690572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Trink B., Okami K., Wu L., Sriuranpong V., Jen J., Sidransky D. A new human p53 homologue. Nat Med. 1998 Jul;4(7):747–748. doi: 10.1038/nm0798-747. [DOI] [PubMed] [Google Scholar]
  32. Vennegoor C. J., Nijman H. W., Drijfhout J. W., Vernie L., Verstraeten R. A., von Mensdorff-Pouilly S., Hilgers J., Verheijen R. H., Kast W. M., Melief C. J. Autoantibodies to p53 in ovarian cancer patients and healthy women: a comparison between whole p53 protein and 18-mer peptides for screening purposes. Cancer Lett. 1997 Jun 3;116(1):93–101. doi: 10.1016/s0304-3835(97)00168-7. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Vojtesek B., Dolezalova H., Lauerova L., Svitakova M., Havlis P., Kovarik J., Midgley C. A., Lane D. P. Conformational changes in p53 analysed using new antibodies to the core DNA binding domain of the protein. Oncogene. 1995 Jan 19;10(2):389–393. [PubMed] [Google Scholar]
  35. Yokomizo A., Mai M., Tindall D. J., Cheng L., Bostwick D. G., Naito S., Smith D. I., Liu W. Overexpression of the wild type p73 gene in human bladder cancer. Oncogene. 1999 Feb 25;18(8):1629–1633. doi: 10.1038/sj.onc.1202474. [DOI] [PubMed] [Google Scholar]
  36. Zaika A. I., Kovalev S., Marchenko N. D., Moll U. M. Overexpression of the wild type p73 gene in breast cancer tissues and cell lines. Cancer Res. 1999 Jul 1;59(13):3257–3263. [PubMed] [Google Scholar]
  37. Zalcman G., Schlichtholz B., Trédaniel J., Urban T., Lubin R., Dubois I., Milleron B., Hirsch A., Soussi T. Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment. Clin Cancer Res. 1998 Jun;4(6):1359–1366. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES