Human epididymis protein 4 antigen‐autoantibody complexes complement cancer antigen 125 for detecting early‐stage ovarian cancer

Background Early detection of ovarian cancer could significantly improve patient outcomes. Cancer antigen 125 (CA 125) is elevated in sera from approximately 60% of patients with early‐stage (I/II) disease. Sensitivity might be improved through the combination of CA 125 with other biomarkers. Among potential biomarkers, antigen‐autoantibody (Ag‐AAb) complexes have received relatively little attention. Methods Luminex‐based immunoassays were used to measure human epididymis protein 4 (HE4), anti‐HE4 autoantibody, and HE4 Ag‐AAb complexes in sera from patients with early‐ (n = 73) and late‐stage ovarian cancers (n = 49) at the time of diagnosis and from asymptomatic women with (n = 15) or without ovarian cancer (n = 212) enrolled in the Normal Risk Ovarian Cancer Screening Study. Results At 98% specificity for healthy, asymptomatic women, 7% of patients with early‐stage (I/II) ovarian cancer and 4% of patients with late‐stage (III/IV) disease had elevated levels of HE4 autoantibody, whereas elevated levels of HE4 Ag‐AAb complexes were detected in sera from 38% of early‐stage cases and 31% of late‐stage cases. Complementarity was observed in receiver operating characteristic (ROC) curves between HE4 Ag‐AAb complexes and CA 125 levels in early‐stage ovarian cancer (P