Urinary Concentrations of Human Epidydimis Secretory Protein 4 (He4) in The Diagnosis of Ovarian Cancer: A Case-Control Study

Objective: To analyze differential diagnostic accuracy of urinary human epidydimis secretory protein 4 (HE4)in patients with ovarian tumors. Materials and methods: In the case-control study 23 patients with ovariancancer, 37 patients with benign ovarian tumors and 18 women in the control group were included. Serum CA125values and urinary concentrations of HE4were assessed quantitatively. Urinary creatinine concentrations andglomerular filtration rate were also determined and used to calculate ratios to HE4.
Results: Higher urinaryHE4 concentrations were observed in patients with late stage ovarian cancer (p=0.001) and also in patients withearly stage ovarian cancer when compared to patients with benign ovarian tumors (p=0.044). On analysis whereall ovarian cancer patients were included, higher diagnostic accuracy was observed with calculated ratio ofHE4 to glomerular filtration rate (GFR) to unchanged urinary HE4 concentrations -AUC 0.861 vs. 0.858. Whendiscriminatory accuracy was calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations,the last demonstrated a higher area under the curve - 0.701 vs. 0.602. The urinary HE4/creatinine ratio hadlower discriminatory characteristics than unchanged concentrations of urinary HE4. However, HE4 serumconcentration was more accurate for discrimination of patients with benign and malignant ovarian tumors whencompared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum HE4 and 0.856 and 0.653 for urinaryHE4 and CA125, respectively).
Conclusions: Ovarian cancer patients have higher urinary concentrations ofhuman epidydimis secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has comparablediscriminatory accuracy with serum HE4 for benign and malignant ovarian tumors and can be recommendedas a non-invasive ovarian cancer risk assessment method.