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Almost three quarters of ovarian cancer cases are diagnosed at advanced stages, making this disease the most lethal gynecologic malignancy in U.S. women. Using sera from a total of 1400 healthy women, and women with early- and late-stage ovarian cancer, investigators evaluated 96 candidate serum proteins to pinpoint and validate a panel of four biomarkers (CA 125, HE4, CEA, and VCAM-1) that best distinguished sera from women with early ovarian malignancies from those of healthy controls. Sensitivity of the biomarker panel was 86% and 95% for identifying early- and late-stage ovarian cancers, respectively, with 98% specificity; moreover, the panel performed substantially better than CA 125 alone.