Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

Background: Ovarian cancer remains a major worldwide health care issue due to the lack of satisfactory diagnostic methods for early detection of the disease. Prior studies on the role of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in detecting ovarian cancer presented conflicting results. New tools to improve the accuracy of identifying malignancy are urgently needed. We here aimed to evaluate the diagnostic utility of tissue CA125 and HE4 gene expression in comparison to serum CA125 and HE4 in discriminating benign from malignant pelvic masses. Materials and
Methods: One-hundred Egyptian women were enrolled in this study, including 60 epithelial ovarian cancer (EOC) patients and 20 benign ovarian tumor patients, as well as 20 apparently healthy women. Preoperative serum levels of CA125 and HE4 were measured by immunoassays. Tissue expression levels of genes encoding CA125 and HE4 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The diagnostic performance of CA125 and HE4, measured either as mRNA or protein levels, was evaluated by receiver operating characteristic (ROC) curves.
Results: The serum CA125+HE4 combination and serum HE4, with area under the curve (AUC) values of 0.935 and 0.932, respectively, performed significantly better than serum CA125 (AUC=0.592; P<0.001). Tissue CA125 and HE4 (AUC=1) performed significantly better than serum CA125 (P<0.001), serum HE4 (P=0.016) and the serum CA125+HE4 combination (P=0.018).
Conclusions: Measurement of tissue CA125 and HE4 gene expression not only improves discriminatory performance, but also broadens the range of differential diagnostic possibilities in distinguishing EOC from benign ovarian tumors.