Patient-derived tumor-reactive antibodies as diagnostic markers for ovarian cancer

Objective. Most ovarian cancers are diagnosed at advanced stage (67%) and prospects for significant improvement in survival reside in early diagnosis. Our objective was to validate our array assay for the identification of ovarian cancer based on quantitation of tumor-reactive IgG. Methods. The diagnostic array utilizes specific exosome-derived antigens to detect reactive IgG in patient's sera. Specific protein targets were isolated by immunoaffinity from exosomes derived from ovarian tumor cell lines. Sera were obtained from age-matched female volunteers, women with benign ovarian disease and with ovarian cancer. Immunoreactivity was also compared between exosomal proteins and their recombinant counterparts. Results. Sera from ovarian cancer patients exhibited significantly greater immunoreactivities than either normal controls or women with benign disease (both considered negative to all antigens tested). Reactivities with nucleophosmin, cathepsin D, p53, and SSX common antigen for patients with all stages of ovarian cancer were significantly higher than for controls and women with benign ovarian disease. Reactivity with placental type alkaline phosphatase, TAG 72, survivin, NY-ESO-1, GRP78, and Muc16 (CA125) allowed the differentiation between Stage III/IV and early stage ovarian cancer. Conclusions. The quantitation of circulating tumor-reactive IgG can be used to identify the presence of ovarian cancer. The analyses of IgG recognition of specific exosomal antigens allows for the differentiation of women with benign ovarian masses from ovarian cancer, as well as distinguishing early and late stage ovarian cancers. Thus, the quantitative assessment of IgG reactive with specific tumor-derived exosomal proteins can be used as diagnostic markers for ovarian cancer. (C) 2009 Elsevier Inc. All rights reserved.