Taylor, D. et al. Patient-derived tumor-reactive antibodies as diagnostic markers for ovarian cancer. Gynecol. Oncol. 115, 112–120 (2009).

The majority of patients with ovarian cancer are generally diagnosed with advanced-stage disease. Despite the advances in chemotherapy, most patients have a poor prognosis due to difficulties in diagnosing the disease. Tumor cells often overexpress specific proteins; as a result, tumor-reactive antibodies can be observed in the circulation of patients soon after initial tumor development and before circulating antigens are detected. Taylor and colleagues assessed autoantibody responses in patients with benign and malignant ovarian lesions—“assessment of this autoantibody response against specific proteins can provide a cancer screening tool superior to those currently available” state the researchers.

Tumor-reactive IgG has been detected in various tumors, including ovarian cancer. Moreover, tumor-reactive IgG can be identified early in tumor development and has been associated with tumor progression. The researchers used a diagnostic array of exosome-derived antigens from human ovarian cancer cell lines to detect reactive IgG in sera obtained from patients with benign and malignant ovarian lesions. Sera were obtained from patients with stage I–IV ovarian cancer and from age-matched healthy female volunteers.

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Taylor and colleagues found significantly greater immunoreactivity in sera from patients with ovarian cancer compared with healthy volunteers or women with benign disease. Sera of patients with early-stage ovarian cancer had a unique, intense immunoreactivity to antigens with molecular weights >100 kDa, whereas sera of patients with late-stage disease had a unique immunoreactivity to antigens with molecular weights <40 kDa. Reactivity with nucleophosmin, cathepsin D, p53 and SSX common antigen was significantly higher in patients with ovarian cancer than healthy individuals and women with benign ovarian disease. Moreover, reactivity with placental type alkaline phosphatase, TAG 72, survivin, NY-ESO-1, GRP78 and CA125 was different in patients with stage III and stage IV disease.

The researchers conclude that quantification of circulating tumor-reactive IgG can be used to detect ovarian cancer, distinguish between benign and malignant ovarian tissue, while also differentiating between early and late-stage disease.