Abstract 2737: Common autoantibodies in ovarian cancer (OvCa) and infertility may define biomarkers for OvCa risk

Abstract

Abstract Background: A 20-year longitudinal study of over 12,000 women shows a higher epidemiologic risk for OvCa and other cancers among women with infertility (Brinton et al, 2005, Epidemiology). In recent studies of an autoimmune etiology for some women with infertility we identified ovarian autoantigens. Several of the autoantigens were also reported as autoantigens in OvCa. Therefore the objective was to determine if there are commonly occurring autoantibodies in sera of women with infertility and OvCa in order to identify a potential risk group that would benefit from closer monitoring and earlier detection of OvCa. Methods: We assessed antibodies to eight recombinant proteins previously identified as OvCa markers or as autoantigens in infertility. Sera (1:100) from women with infertility (n=28), malignant OvCa (n=21), benign ovarian tumors (n=9) and healthy control women without cancer (n=6) were assessed against the antigens (50 ng/well) in standard immunoassays. The antigens included mesothelin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), protein disulfide-isomerase A3 (PDIA3), Selenium Binding Protein 1 (SBP1), aldehyde dehydrogenase 1A1 (ALDH1), aldehyde dehydrogenase 3A1 (ALDH3), alpha-enolase and vimentin. Positive values were those 2 standard deviations above the mean control optical density value (p<0.05). Results: Antibodies to individual antigens in infertility recognized mesothelin (57%), GAPDH (43%), vimentin (43%), enolase (29%), PDIA3 (39%), SBP1 (43%), ALDH1 (46%) and ALDH3 (50%). Results were similar in OvCa for antibodies to mesothelin (33%), GAPDH (38%), vimentin (29%), enolase (29%), PDIA3 (33%), SBP1 (24%), ALDH1 (24%) and ALDH3 (38%). Only enolase antibodies (33%) were found in sera of women with benign tumors. The frequency distribution showed that benign tumor sera reacted with 0 or 1 antigen, women with infertility had peaks at 0, 4 or 6-8 antigens and OvCa sera had peaks at 0, and 5-8 antigens. Conclusions and Significance: We have demonstrated antibodies to 8 ovarian autoantigens in sera from a high frequency of women with OvCa or infertility, a group with increased risk for OvCa. This suggests that assaying for antibodies to such antigens could be used for screening risk groups towards early detection of OvCa. Infertility affects over 10% of reproductive age women. These women are at increased risk of developing OvCa based on current epidemiological data and represent a sizable segment of the population. They would benefit from risk assessment and routine screening for early detection of OvCa. Support: JL: NIH R01AI 055060, Ovarian Cancer SPORE (P50CA83636) Development Award, Segal Women's Cancer Award; IH & JL: NIH R01CA134487 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2737.