HE4 - Human epididymal protein 4

SI UNITS (recommended)


* The SI unit is the recommended method of reporting clinical laboratory results

Units of measurement
nmol/L, pmol/L

The human epididymal protein 4 (HE4, also known as WFDC2) belongs to the family of whey acidic four - disulfide core (WFDC) proteins with suspected trypsin inhibitor properties. The corresponding gene codes for a 13 kD protein. In its mature glycosylated form the protein has a molecular weight of approximately 20‑25 kD and consists of a single peptide chain containing two WFDC domains.

HE4 was first determined in the epithelium of the distal epididymis. It shows low expression in epithelia of respiratory and reproductive tissues including ovary, but high expression in ovarian cancer tissue. High secreted levels can also be found in the serum of ovarian cancer patients. HE4 is also expected to help in the risk assessment of epithelial ovarian cancer.

Ovarian cancer is the fourth most common cause of cancer - related death in women worldwide. It is the most lethal form of gynecological cancer, and potentially curable if diagnosed early and treated by surgeons familiar with the management of ovarian cancer. However, the symptoms of ovarian cancer are related to the presence of adnexal masses and are often vague and unspecific. Thus, 70‑75 % of ovarian cancers are detected at a late stage. According to the International Agency for Research on Cancer, the 5 year survival rate of ovarian cancer patients is 46 %. However, if the disease is diagnosed early, the survival rate increases up to 94 %.

As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially in stage I disease, the early non - symptomatic stage. Combined, CA 125 and HE4 yielded the highest sensitivity with 76.4 % at 95 % specificity. Additionally, HE4 is more sensitive in early - stage endometrial cancer compared to CA 125. Elevated serum HE4 with normal CA 125 would suggest the presence of either ovarian or other type of cancer, for example endometrial cancer.

Combined with other markers such as CA 125, HE4 can help determining whether a pelvic mass is benign or malignant in pre - and post - menopausal women. 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. HE4 levels correlate with clinical response to therapy or recurrence status in women with diagnosis of ovarian carcinoma as determined by CT imaging. HE4 could thus be an important early indicator for disease recurrence.

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