Objective To evaluate the role of the novel tumor marker human epididymal secretory protein E4 (HE4) in discriminating ovarian cancer from benign pelvic disease in patients with a pelvic mass.

Methods Serum samples from 131 patients with epithelial ovarian cancer (EOC) and 126 patients with various benign pelvic diseases were collected preoperatively and tested for cancer antigen (CA)125 and HE4 levels. Receiver operator characteristic curves were constructed, and the area under the curve (AUC) was compared between the markers.

Results The median CA125 and HE4 levels were significantly higher in the patients with EOC than in those with benign disease (P < 0.001). Using benign controls as the comparison group for all cases, the AUC for combined HE4 and CA125 (0.955) was significantly higher than that for HE4 (0.941) or CA125 alone (0.924; P < 0.05). A comparison of premenopausal benign controls to EOC cases showed that the AUC for combined HE4 and CA125 (0.97) was significantly higher than that for CA125 (0.93; P < 0.004). The AUC for HE4 was significantly higher compared to that of CA125 in discriminating EOC from ovarian endometriosis (0.969 vs 0.904; P = 0.014) and pelvic inflammatory disease (0.909 vs 0.819; P = 0.034).

Conclusion Serum HE4 testing is a more powerful tool than CA125 assay to discriminate EOC from ovarian endometriosis and pelvic inflammatory disease. For patients with a pelvic mass, especially premenopausal patients, the serum concentration of HE4 adds valuable information to CA125 in identifying patients with EOC from those with benign pelvic disease.