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p53-autoantibody may be more sensitive than CA-125 in monitoring microscopic and macroscopic residual disease after primary therapy for epithelial ovarian cancer

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Abstract

Purpose

To evaluate the use of p53-autoantibodies (p53-aab) for monitoring minimal disease after standard therapy of advanced epithelial ovarian cancer (EOC).

Methods

Retrospective analysis of p53-aab in preoperative and long-term follow-up serum samples from 10 patients selected for representing three relevant EOC subgroups: platinum-sensitive disease after macroscopic complete debulking (n = 4) and platinum-sensitive (n = 3) or platinum-resistant disease (n = 3), both after suboptimal debulking with residual tumor of <1 cm diameter. p53-aab levels were quantified by a sandwich ELISA in two independent experiments. CA-125 values of all samples and clinical information were retrieved from medical records.

Results

Patients with early relapse (median PFS 7 months, n = 8) had high p53-aab levels throughout follow-up while CA-125 values had dropped below the cut-off after primary surgery during or after chemotherapy in these cases. Patients with seroconversion to p53-aab negativity experienced prolonged PFS (n = 2; #1: 50 months, #2: no evidence of disease for 36 months until last follow-up). Continued p53-aab positivity was not related to the resection status or platinum sensitivity.

Conclusions

p53-autoantibodies may be a highly sensitive marker for minimal residual tumor mass after surgery and/or chemotherapy rather than standard CA-125, possibly due to the different nature of these markers. CA-125 released by cancer cells is related to tumor mass, whereas p53-aab levels can indicate the presence of few tumor cells due to amplification by the immune system. Seroconversion of p53-aab could be associated with long-term survival.

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References

  • Anderson KS, LaBaer J (2005) The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res 4(4):1123–1133

    Article  PubMed  CAS  Google Scholar 

  • Bauerschlag DO, Schem C, Weigel MT et al (2010) The role of p53 as a surrogate marker for chemotherapeutical responsiveness in ovarian cancer. J Cancer Res Clin Oncol 136(1):79–88

    Article  PubMed  CAS  Google Scholar 

  • Burger RA, Brady MF, Bookman MA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483

    Article  PubMed  CAS  Google Scholar 

  • Cramer DW, Bast RC Jr, Berg CD et al (2011) Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 4(3):365–374

    Article  Google Scholar 

  • Gadducci A, Ferdeghini M, Buttitta F et al (1998) Serum anti-p53 antibodies in the follow-up of patients with advanced ovarian carcinoma. Anticancer Res 18(5B):3763–3765

    PubMed  CAS  Google Scholar 

  • Gumus E, Erdamar S, Demirel G et al (2004) Association of positive serum anti-p53 antibodies with poor prognosis in bladder cancer patients. Int J Urol 11(12):1070–1077

    Article  PubMed  Google Scholar 

  • Hori SS, Gambhir SS (2011) Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med 3(109):109ra116

    Google Scholar 

  • Lu D, Kuhn E, Bristow RE et al (2011) Comparison of candidate serologic markers for type I and type II ovarian cancer. Gynecol Oncol 122(3):560–566

    Article  PubMed  CAS  Google Scholar 

  • Lu H, Ladd J, Feng Z et al (2012) Evaluation of known oncoantibodies, HER2, p53, and cyclin B1, in prediagnostic breast cancer sera. Cancer Prev Res (Phila) 5(8):1036–1043

    Article  CAS  Google Scholar 

  • Mastropaolo W, Fernandez Z, Miller EL (1986) Pronounced increases in the concentration of an ovarian tumor marker, CA-125, in serum of a healthy subject during menstruation. Clin Chem 32(11):2110–2111

    PubMed  CAS  Google Scholar 

  • Mongia SK, Rawlins ML, Owen WE et al (2006) Performance characteristics of seven automated CA 125 assays. Am J Clin Pathol 125(6):921–927

    Article  PubMed  CAS  Google Scholar 

  • Pedersen JW, Gentry-Maharaj A, Fourkala EO et al. (2012) Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer. Br J Cancer doi:10.1038/bjc.2012.517

  • Perren TJ, Swart AM, Pfisterer J et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496

    Article  PubMed  CAS  Google Scholar 

  • Riedinger JM, Wafflart J, Ricolleau G et al (2006) CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol 17(8):1234–1238

    Article  PubMed  CAS  Google Scholar 

  • Rohayem J, Conrad K, Zimmermann T et al (1999) Comparison of the diagnostic accuracy of three commercially available enzyme immunoassays for anti-p53 antibodies. Clin Chem 45(11):2014–2016

    PubMed  CAS  Google Scholar 

  • Soussi T (2000) p53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Res 60(7):1777–1788

    PubMed  CAS  Google Scholar 

  • Takeda A, Shimada H, Nakajima K et al (2001) Monitoring of p53 autoantibodies after resection of colorectal cancer: relationship to operative curability. Eur J Surg 167(1):50–53

    Article  PubMed  CAS  Google Scholar 

  • Tan HT, Low J, Lim SG et al (2009) Serum autoantibodies as biomarkers for early cancer detection. FEBS J 276(23):6880–6904

    Article  PubMed  CAS  Google Scholar 

  • Vogl FD, Frey M, Kreienberg R et al (2000) Autoimmunity against p53 predicts invasive cancer with poor survival in patients with an ovarian mass. Br J Cancer 83(10):1338–1343

    Article  PubMed  CAS  Google Scholar 

  • Zalcman G, Schlichtholz B, Tredaniel J et al (1998) Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment. Clin Cancer Res 4(6):1359–1366

    PubMed  CAS  Google Scholar 

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Conflict of interest

MF is employed by Steinbeis-Transferzentrum commercializing the p53-AAB ELISA. The Steinbeis-Transferzentrum had no influence on data acquisition, analysis or interpretation and manuscript drafting. All other authors have no conflict of interest to disclose.

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Correspondence to Ingo B. Runnebaum.

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Häfner, N., Nicolaus, K., Weiss, S. et al. p53-autoantibody may be more sensitive than CA-125 in monitoring microscopic and macroscopic residual disease after primary therapy for epithelial ovarian cancer. J Cancer Res Clin Oncol 139, 1207–1210 (2013). https://doi.org/10.1007/s00432-013-1432-2

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  • DOI: https://doi.org/10.1007/s00432-013-1432-2

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