Abstract 4471: Autoantibodies in infertility are associated with ovarian cancer
Authors: Yi Yu, Jee Eun Nam, Seby L. Edassery, Ingegerd Hellstrom, Karl E. Hellstrom, Nicole Urban, Judith L. Luborsky
Journal: Cancer Research (2012)

Abstract Epidemiological studies show women with infertility have increased ovarian cancer (OvCa) risk, but biomarkers indicating which women are at increased risk are unavailable. We showed autoantibodies (Abs) are associated with infertility suggesting an autoimmune etiology in some women. While CA125 remains the most frequently used OvCa biomarker, it has limited sensitivity and specificity, and additional biomarkers predicting early OvCa remain to be determined. We sought to determine if Abs to Selenium Binding Protein 1 (SBP1) associated with infertility are also found in OvCa; if Abs to mesothelin (MSLN), a well characterized circulating OvCa tumor antigen, occur in infertility; and if these Abs differed from CA125. CA125 was measured by an established bead-based assay and anti-MSLN and anti-SBP1 Abs were measured by immunoassay using sera from OvCa patients (n=28), women with infertility (n=109; including endometriosis, ovulatory dysfunction, unexplained infertility and Premature Menopause (POF), benign ovarian tumors or cysts (n=24), healthy women (n=152) and assay controls (n=16). CA125 was significantly higher in early (p=0.039) and late OvCa (P=0.003) compared to controls. CA125 was also elevated in some women with endometriosis and unexplained in fertility but overall was not significantly different from controls. Anti-MSLN Abs were significantly more frequent in women with prematurely reduced ovarian function including ovulatory dysfunction (65%), POF (52%) and unexplained infertility (32%) compared to controls. Women with endometriosis, who also have a high OvCa risk, did not have anti-MSLN Abs. Anti-SBP1 Abs were significantly higher and more frequent in the same categories of infertility that were positive for anti-MSLN Abs, but not in the same women. SBP1 Abs occurred in ovulatory dysfunction (50%), POF (27%) and unexplained infertility (32%) compared to healthy controls. Anti-MSLN Abs occurred in early (14%) and late (9%) OvCa and anti-SBP Abs occurred in early (17%) and late (20%) OvCa. Anti-MSLN and anti-SBP were not correlated (Spearman's correlation coefficient, 0.14, p=0.12) suggesting they might complement each other. CA125 was correlated with MSLN (0.27, p=0.001) overall and within cancer only (0.50, p=0.015), but was not correlated with anti-MSLN (all: 0.036, p=0.65, OvCa: 0.3, p=0.13) or anti-SBP (all: 0.01, p=0.92, OvCa: 0.10, p=0.61), which suggests they might complement CA125 in a panel for detection of early OvCa detection. We demonstrate for the first time that antibodies to MSLN and SBP1 occur in both infertility and OvCa suggesting these biomarkers may indicate OvCa risk. The results also suggest autoantibodies may complement measurement of CA125. Thus, identification of antibody biomarkers in a high risk, pre-diagnostic group may provide novel biomarkers for early OvCa. Support: DOD OC073325 (JL), NIH R01 CA134487 (IH&amp;JL) and P50 CA083636 (NU). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4471. doi:1538-7445.AM2012-4471