Detection of autoantibodies to multiple tumor-associated antigens in the immunodiagnosis of ovarian cancer

Ovarian cancer is one of the most common cancers in women. Its early stages may be asymptomatic, and as a result diagnosis frequently occurrs at an advanced, often incurable, stage. The high mortality and low survival rates associated with ovarian cancer can in part be attributed to the lack of diagnostic methods allowing for early detection, yet a methodology to identify patients with early-stage ovarian cancer remains to be established. In order to investigate the frequency of antibodies against a panel of multiple carefully-selected tumor-associated antigens (TAAs) in sera from patients with ovarian cancer, and to determine the possibility and usefulness of such a panel of TAAs in the immunodiagnosis of ovarian cancer, sera from 32 ovarian cancer patients and 82 normal individuals were tested using an enzyme-linked immunosorbent assay (ELISA) for the presence of autoantibodies to a panel of 13 TAAs. ELISA results were also confirmed by immunoblotting analysis. The sensitivity and specificity of the multiple anti-TAA antibodies in the detection of ovarian cancer was 62.5 and 85.4%, respectively. With the successive addition of TAAs to a total of 7 antigens (survivin, p53, p16, cyclin B1, cyclin D1, cyclin A and cyclin E), there was a stepwise increase in sensitivity of up to 62.5%, and in specificity of 90.2%. With the addition of more antigens to the panel, no further increase in sensitivity was detected. This study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of cancer, and also indicates that, in the selection of ovarian cancer-associated TAAs, some may be specific to ovarian cancer while others may not be. This emphasizes the importance of a comprehensive analysis of antibody response to selected TAAs in various disease conditions, such as ovarian cancer, in benign ovarian diseases, and in normal individuals, before conclusions can be drawn regarding their contribution to ovarian cancer.