Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer

  • Raluca A. Budiu
  • Gina Mantia-Smaldone
  • Esther Elishaev
  • Tianjiao Chu
  • Julia Thaller
  • Kathryn McCabe
  • Diana Lenzner
  • Robert P. Edwards
  • Anda M. Vlad
Original article

Abstract

MUC1 (CA15-3) and MUC16 (CA125) tumor-associated antigens are upregulated in ovarian cancer and can be detected in patients’ sera by standardized tests. We postulated that increased MUC1 and MUC16 antigens augment antibody responses in platinum-resistant ovarian cancer patients and that the frequency and intensity of these responses can be used as immune biomarkers of treatment response and disease outcome. We measured MUC1 and MUC16 tumor expression by immunohistochemistry (IHC), assessed serum antigenic levels and quantitated circulating antibodies by ELISA in a cohort of 28 ovarian cancer patients with platinum-resistant or platinum-refractory ovarian cancer, and treated with intraperitoneal (IP) interleukin-2 (IL-2). MUC1 and MUC16 were overexpressed in tumor samples and showed differential distribution profiles. Serum MUC1 (CA15-3) measurements were elevated in all patients and significantly correlated with increased risk of death (P = 0.003). MUC1-specific IgM and IgG anitbodies were found in 92 and 50% of cases, respectively. Patients with progressive disease had higher mean anti-MUC1 IgG than responders at both early (P = 0.025) and late (P = 0.022) time points during IP IL-2 treatment. Anti-MUC1 IgM antibodies inversely correlated with overall survival at both early (P = 0.052) and late (P = 0.009) time points. In contrast to MUC1, neither soluble MUC16 nor MUC16-specific antibodies were significantly associated with clinical response or overall survival in this study. Increased serum MUC1 and high anti-MUC1 antibody levels are prognostic for poor clinical response and reduced overall survival in platinum-resistant or platinum-refractory ovarian cancer.

Keywords

Ovarian cancer Platinum resistance MUC1 (CA15-3) MUC16 (CA125) Humoral immunity Interleukin-2 Biomarkers 

Supplementary material

262_2011_1010_MOESM1_ESM.ppt (2.4 mb)
Supplementary material 1 (PPT 2482 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Raluca A. Budiu
    • 1
    • 2
  • Gina Mantia-Smaldone
    • 3
  • Esther Elishaev
    • 1
    • 4
  • Tianjiao Chu
    • 2
  • Julia Thaller
    • 2
  • Kathryn McCabe
    • 2
  • Diana Lenzner
    • 5
  • Robert P. Edwards
    • 1
    • 2
  • Anda M. Vlad
    • 1
    • 2
  1. 1.Department of Obstetrics, Gynecology, and Reproductive Sciences, School of MedicineUniversity of PittsburghPittsburghUSA
  2. 2.Magee-Women’s Research InstitutePittsburghUSA
  3. 3.Division of Gynecologic OncologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Pathology, Magee-Women’s HospitalUniversity of Pittsburgh Medical CenterPittsburghUSA
  5. 5.University of Pittsburgh Cancer InstitutePittsburghUSA

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