title: Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer.
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.
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA 15213, USA.
authors: Raluca A
authors: RA
authors: Budiu
authors: Gina
authors: G
authors: Mantia-Smaldone
authors: Esther
authors: E
authors: Elishaev
authors: Tianjiao
authors: T
authors: Chu
authors: Julia
authors: J
authors: Thaller
authors: Kathryn
authors: K
authors: McCabe
authors: Diana
authors: D
authors: Lenzner
authors: Robert P
authors: RP
authors: Edwards
authors: Anda M
authors: AM
authors: Vlad
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000276:immunology*; D018394:CA-125 Antigen / Q000276:immunology*; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000276:immunology; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000627:therapeutic use; D008565:Membrane Proteins / Q000276:immunology*; D018396:Mucin-1 / Q000276:immunology*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology*; D011379:Prognosis
chemical_list: D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D007376:Interleukin-2; C060192:MUC1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D009944:Organoplatinum Compounds