An ovarian cancer malignancy risk index composed of HE4, CA125, ultrasonographic score, and menopausal status: use in differentiation of ovarian cancers and benign lesions.

A case-control study included 83 ovarian cancer patients, 76 patients with benign ovarian tumors, and 79 healthy control subjects in the control group. Objective of the study is to analyze biomarker concentrations included in the two novel ovarian tumor differential diagnostic tests (risk of ovarian malignancy algorithm and OVA1) approved by food and drug administration in patients with ovarian tumors and to establish a new ovarian cancer risk assessment algorithm in conjunction with ultrasound score and menopausal status. Ovarian cancer diagnostic tests, developed in the training setting, were evaluated in the independent validation settings of Asian Pacific ovarian cancer biomarker research group study population and Denmark Pelvic Mass project population. Results show that mean serum concentrations of cancer antigen 125 (CA125), human epididymis secretory protein 4 (HE4), and beta-2-microglobulin were upregulated, but apolipoprotein A1, transferrin, and transthyretin were downregulated among ovarian cancer patients. When only one biomarker was introduced in the logistic regression analysis, together with ultrasonographic score and menopausal status, HE4 (area under the curve (AUC) = 0.930; 95 % confidence interval (CI) 0.891-0.969) was more accurate than CA125 (AUC = 0.902; 95 % CI 0.855-0.949) in ovarian cancer diagnostic, but when both biomarkers were included in the logistic regression analyses, ovarian cancer diagnostic accuracy was increased (AUC = 0.939; 95 % CI 0.902-0.977). In conclusions, human epididymis secretory protein 4 and CA125 in combination with ultrasonographic features and menopausal status has high accuracy in ovarian tumor differentiation.