Simmons AR, et al. - Researchers explored the sensitivity and lead time of a multi-marker panel (CA125, HE4, MMP-7, and CA 72-4) vs CA125 alone in the early detection of ovarian cancer. Pre-clinical longitudinal specimens from 75 women (50 screen-positive, 25 screen-negative) who developed invasive epithelial ovarian cancer (3-5 serial specimens each) and 547 healthy controls (1-10 serial specimens each) from an ovarian cancer screening trial were included in a blinded fashion. Utilizing multiplexed bead-based immunoassays with low detection limits, high inter- and intra-assay precision, negligible cross-reactivity and good correlation with standard immunoassays, they estimated the multi-marker concentrations in ultra-low serum volumes (16 µL). MMP-7 identified none whereas HE4 and CA72-4 classified 16% of screen-negative cases at 98% specificity. They confirmed HE4 and CA72-4 as complementary biomarkers to CA125 for longitudinal screening.