HE4 Ovarian Biomarker

Ovarian cancer is the 4th leading cause of cancer death worldwide and responsible for 5% for all cancer deaths in women. More than 200,000 women are annually diagnosed with ovarian cancer and fewer than 30% of these ovarian cancers are diagnosed in stages I / II.

The gene encoding HE4 is amplified in ovarian carcinomas, whereas its expression in normal tissues, including ovary, is low. The function of the HE4 protein (Human Epididymis protein 4) is currently unknown, but compared to CA 125 its specificity for malignant disease is higher. 

Another advantage of HE4 is that it only shows higher concentrations in women with endometrial and ovarian cancer, however not with ovarian endometriomas or other types of endometriosis. Measuring the combination of both markers can be used to classify women with tumors into high and low risk groups and to estimate the risk of epithelial ovarian cancer in premenopausal and postmenopausal women presenting with pelvic mass (using the ROMA™ - Risk of Ovarian Malignancy Algorithm).

HE4 and CA 125 are complementary markers and their combined use increases diagnostic accuracy for all age groups. By measuring both markers together the strengths of both markers can be combined to ensure optimized sensitivity and specificity for primary diagnosis – especially for patients with pelvic mass and detection of recurrence during follow-up.

The dual marker combination CA 125 and HE4 is a more accurate predictor of malignancy than either alone. Huhtinen et al. reported a 78.6% sensitivity at 95% specificity in ovarian carcinoma vs. endometriotic cysts.

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