Skip to main content
Log in

Circulating p53 Antibody in Patients with Colorectal Cancer

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I–IIIb/Dukes classification A–C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Hollstein M, Sidransky D, Vogelstein B, Harris CC: p53 mutation in human cancers. Science 253:49-53, 1991

    PubMed  Google Scholar 

  2. Soussi T, Legros Y, Lubin R, Ory K, Schlichtholz B: Multifunctional analysis of p53 alteration in human cancer: a review. Int J Cancer 57:1-9, 1994

    PubMed  Google Scholar 

  3. Kern SE, Hamilton SR, Vogelstein B: Clinical implications of colorectal tumor. In Molecular Foundations of Oncology. S Broder (ed). New York, Williams & Wilkins, 1991, pp 381-390

    Google Scholar 

  4. Rogel A, Popliker M, Webb CG, Oren M: p53 cellular tumor antigen: Analysis of mRNA levels in normal adult tissues, embros, and tumors. Mol Cell Biol 5:2851-2855, 1985

    PubMed  Google Scholar 

  5. Gannon JV, Greaves R, Iggo R, Lane DP: Activating mutations in p53 produces a common conformational effect-a monoclonal antibody specific for the mutant form. EMBO J 9:1595-1623, 1990

    PubMed  Google Scholar 

  6. Hsu H-C, Tseng H-J, Lai P-H, Peng S-Y: Expression of p53 gene in 184 unifocal hepatocellular carcinoma: Association with tumor growth and invasiveness. Cancer Res 53:4691-4694, 1993

    PubMed  Google Scholar 

  7. Hall PA, Ray A, Lemine NR, Midgley CA, Krausz T, Lane DP: p53 immunostaining as a marker of malignant disease in diagnostic cytopathology. Lancet 338:513, 1991

    PubMed  Google Scholar 

  8. Cattoretti G, Rilke F, Andrealo S, D'amato L, Delia D: p53 expression in breast cancer. Int J Cancer 41:178-183, 1988

    PubMed  Google Scholar 

  9. Crawford LV, Pim DC, Bulbrook RD: Detection of antibodies against cellular protein p53 in sera from patients with breast cancer. Int J Cancer 30:403-408, 1982

    PubMed  Google Scholar 

  10. Sclichtholz 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 52:6380-6384, 1992

    PubMed  Google Scholar 

  11. Davidoff AM, Iglehart JD, Marks JR: Immune response to p53 is dependent on p53/HSP70 complexes in breast cancers. Proc Natl Acad Sci USA 89:6380-6384, 1992

    Google Scholar 

  12. Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF, Carbone DP: Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 52:4168-4174, 1992

    PubMed  Google Scholar 

  13. Lubin R, Sclichtholz RLB, Bengoufa D, Zalcman BG, Tredaniel J, Hirsch A, Caron de Fromental C, Preudhomme C, Fenaux P, Fournier G, Mangin P, Laurent-Puig P, Pelletir G, Schlumberger M, Desgrandchamps F, Duc AL, Peyrat JP, Janin N, Bressac B, Soussi T: 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 53:5872-5876, 1993

    PubMed  Google Scholar 

  14. Caron De Fronmentel C, May-Levin F, Mouriesse H, Chanrasekaran K, May P: Presence of circulating antibodies against cellular protein p53 in a notable proportion of children with B-cell lymphoma. Int J Cancer 39:185-189, 1987

    PubMed  Google Scholar 

  15. Volkmann M, Müller M, Hoffman WJ, Meyer M, Hagelstein J, Räth U, Kommerrell B, Zentgraf H, Galle PR: The humoral immune response to p53 in patients with hepatocellular carcinoma is specific for malignancy and independent of the a fetoprotein. Hepatology 18:559-565, 1993

    PubMed  Google Scholar 

  16. 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 27:661-668, 1997

    PubMed  Google Scholar 

  17. Peyrat J-P, Bonnetterre J, Lubin R, Vanlemmens L, Fournier J, Souussi T: Prognostic significance of circulating p53 antibodies in patients undergoing surgery for coloregional breast cancer. Lancet 345:621-622, 1995

    PubMed  Google Scholar 

  18. Angelopoulou K, Rosen B, Stratis M, Yu H, Solomou M, Diamandis EP: Circulating antibodies against p53 protein in patients with ovarian carcinoma. Cancer 78:2146-2152, 1996

    PubMed  Google Scholar 

  19. Japanese Society for Cancer of the Colon and Rectum: In General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus. Tokyo, Kinbara, Inc., 1994, pp 33-35

    Google Scholar 

  20. Gabriel WB, Dukes C, Bussey HJR: Lymphatic spread an cancer of the rectum. Br J Surg 23:395-413, 1936

    Google Scholar 

  21. Houbiers JGA, van der Burg SH, van de Watering LMG, Tollenaar RAEM, Brand A, van de Velde VJH, Melief CJM: Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Cancer 72:637-664, 1995

    PubMed  Google Scholar 

  22. Ishida M, Gomyo Y, Ohfuji S, Ikeda M, Ito H, Kawasaki H: Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in human gastric intestinal-type carcinoma in vitro. Jpn J Cancer Res 88:468-475, 1997

    PubMed  Google Scholar 

  23. Fearon ER, Vogelstein B: A genetic model for colorectaltumorigenesis. Cell 61:759-767, 1990

    Google Scholar 

  24. Levine AJ, Momand J, Finlay CA: The p53 tumour supressor gene. Nature 351:453-456, 1991

    PubMed  Google Scholar 

  25. Hamelin R, Laurent-Puig P, Plschwang S, Jego N, Asselain B, Remvikos Y, Girodet J, Salmon RJ, Thomas G: Association of p53 mutation with short survival in colorectal cancer. Gastroenterology 106:42-48, 1994

    PubMed  Google Scholar 

  26. Sun X-F, Vcarstensen JM, Stal O, Zhang H, Nilsson E, Sjodahl R, Nordensjold B: Prognostic significance of p53 expression in relation to DNA ploidy in colorectal adenocarcinoma. Virchow Arch (A) 423:443-448, 1993

    Google Scholar 

  27. Yamaguchi A, Kurosaki Y, Fushida S, Kanno M, Yonemura Y, Miwa K, Miyazaki I: Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis. Cancer 70:2778-2784, 1992

    PubMed  Google Scholar 

  28. Levine AJ, Momand A, Finlay CA: The p53 tumor suppressor gene. Nature 358:453-456, 1992

    Google Scholar 

  29. Davidoff AM, Igelehart JD, Marks JR: Immune response to p53 is dependent upon p53 HSP 70 complexes in breast cancer. Proc Natl Acad Sci USA 89:3439-3442, 1992

    PubMed  Google Scholar 

  30. Coomber D, Hawkins NJ, Clark M, Meagher A, Ward RL: Characterisation and clinicopathological correlates of serum anti-p53 antibodies in breast and colon cancer. J Cancer Res Clin Oncol 122:757-762, 1996

    PubMed  Google Scholar 

  31. Benjamin BL, David MB, Norman Z, Anthony MS, Richard AH: Diagnosis and prognosis in colon cancer based on a profile of immune reactivity. J Natl Cancer Inst 54:319-325, 1975

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shiota, G., Ishida, M., Noguchi, N. et al. Circulating p53 Antibody in Patients with Colorectal Cancer. Dig Dis Sci 45, 122–128 (2000). https://doi.org/10.1023/A:1005473729976

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005473729976

Navigation