Serum human epididymal protein 4 (HE4) as biomarker for the differentiation between epithelial ovarian cancer and ovarian metastases of gastrointestinal origin

• Serum HE4 is less frequently elevated in patients with ovarian metastases from gastrointestinal origin compared to patients with ovarian cancer.
• HE4 can be used in combination with CEA to differentiate preoperatively between ovarian cancer and ovarian metastases from GI origin.
• HE4^2.5/CEA-ratio showed the best discriminative potential for identifying ovarian cancer in a group of patients with a malignant ovarian mass.

ObjectiveAbout 5–15% of all malignant ovarian tumors are metastases from other malignancies such as gastrointestinal tumors, breast cancer or melanoma. Also other gynecological tumors can metastasize to the ovaries. It is crucial to differentiate between primary epithelial ovarian cancer (EOC) and ovarian metastases because different treatment is required. The clinical value of human epididymal secretory protein 4 (HE4) as a serum biomarker in primary ovarian cancer has been established. The use of HE4 in the differentiation between primary ovarian cancer and ovarian metastases from other malignancies has never been investigated.MethodsHE4, CA125 and CEA were measured in 192 patients with EOC (n = 147) or ovarian metastases (n = 40). Univariate and multivariate logistic regression analyses were done. Sensitivity, specificity and area under the curve (AUC) were calculated for all markers and ratios hereof using receiver operating characteristics methodology.ResultsMedian serum HE4 concentration was significantly higher in patients with EOC compared to patients with ovarian metastases (431 pmol/L vs 68 pmol/L, p < 0.001). HE4 and CEA were independent factors in differentiating between EOC and ovarian metastases (both p < 0.001) while CA125 was not (p = 0.33). The HE42.5/CEA ratio demonstrated the highest discriminative value (ROC-AUC 0.94) compared to HE4, CEA, CA125 or CA125/CEA ratio (0.88, 0.78, 0.80 and 0.89 respectively) and showed a specificity of 82.5% at set sensitivity of 90% in discriminating EOC from ovarian metastases.ConclusionHE4 can be used in combination with CEA to make the distinction between EOC and ovarian metastases from gastrointestinal origin.