CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels.

Abstract

BackgroundCA125 is the most widely used serum marker for preoperative diagnosis of ovarian cancer. However, CA125 elevation is not specific to ovarian cancer. More than 60% of patients who have elevated CA125 levels do not have ovarian cancer. To overcome the low specificity of CA125, we identified a CA125 glycoform that was specifically elevated in ovarian cancer and that may help in the further triage of patients with elevated serum CA125 levels.MethodsWe used antibody-lectin ELISA to detect various CA125 glycoforms. Among 21 lectins tested, VVA, a plant lectin that preferentially binds Tn antigen, showed significantly stronger binding with ovarian cancer-derived CA125 than benign condition-derived CA125. CA125-Tn levels were tested among patients with elevated CA125 levels (n=328, including 68 ovarian cancer, 15 ovarian borderline tumors, and 245 benign conditions). The efficacy of CA125-Tn in diagnosing ovarian cancer was evaluated using ROC analysis.ResultsMedians and 25th to 75th quartiles of CA125-Tn levels were 0.31 (0.18–0.65) in ovarian cancer, 0.07 (0.02–0.12) in ovarian borderline tumor, and 0.07 (0.01–0.12) in benign conditions. AUC of the ROC curve was 0.890 (95% CI: 0.845, 0.935) for CA125-Tn to discriminate ovarian cancer cases from nonmalignant cases (borderline tumors and benign conditions). Its performance was even better among patients older than 45 y (AUC: 0.905, 95% CI: 0.841, 0.969). Specificity was improved from 35.1% for CA125 to 75.7% for CA125-Tn among patients older than 45 y when sensitivity was fixed at 90%.ConclusionsCA125-Tn ELISA assay can improve specificity of the preoperative diagnosis of ovarian cancer and serve as a further triage strategy for patients with elevated CA125 levels.