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HelpTest Code HE4 Human Epididymis Protein 4, Serum
Reporting Name
HE4, SUseful For
Aiding in monitoring patients with treated epithelial ovarian cancer for recurrence or progression
This test should not be used as a screening test for ovarian cancer.
Method Name
Electrochemiluminescence Immunoassay (ECLIA)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
SerumSpecimen Required
Patient Preparation: For 12 hours before specimen collection, patient should not take multivitamins or dietary supplements (eg, hair, skin, and nail supplements) containing biotin (vitamin B7).
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
0.75 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Frozen (preferred) | 84 days | |
| Refrigerated | 7 days |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | OK |
Reference Values
Females: ≤140 pmol/L
Males: Not applicable
Day(s) Performed
Monday through Saturday
CPT Code Information
86305
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| HE4 | HE4, S | 55180-4 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| HE4 | HE4, S | 55180-4 |
Clinical Information
Human epididymis (HE) protein 4 belongs to the family of whey acidic four-disulfide core (WFDC) proteins. Currently, the biologic function of HE4 is unknown.
Human epididymis protein 4 has been shown to be overexpressed in 93% of serous, 100% of endometrioid, and 50% of clear cell ovarian carcinomas. In a study of 233 patients with a pelvic mass, including 67 with epithelial ovarian cancer, HE4 had a higher sensitivity for ovarian cancer detection than cancer antigen (CA) 125, 72.9% versus 43.3%, respectively, at a specificity of 95%. Researchers also found HE4 to be elevated in more than half of the ovarian cancer patients who did not have elevated CA 125 levels; therefore, the combination of markers provided slightly improved cancer diagnostic sensitivity for the detection of ovarian cancer.
The main established application of HE4 is in post-therapy monitoring of ovarian cancer patients, who had elevated pretreatment levels. In this setting, it complements CA 125 measurement and facilitates follow-up of patients with little or no CA 125 pretreatment elevations.
Certain histological types of ovarian cancer (mucinous or germ cell tumors) rarely express HE4, therefore the use of HE4 is not recommended for monitoring of patients with these types of ovarian cancer.
Interpretation
Increase in human epididymis protein 4 (HE4) suggests recurrence or disease progression, while a decrease suggests therapeutic response. A change in serum HE4 concentration of greater than or equal to 20% is considered significant.
Cautions
Results cannot be interpreted as absolute evidence of the presence or absence of malignant ovarian disease, because mild elevations of human epididymis protein 4 (HE4) might also be present in individuals with benign gynecologic conditions (ovarian cysts, cystadenomas, leiomyomas, myomas, fibromas, and endometriosis), hypertension, congestive heart failure, and kidney or liver disease.
Serial testing for patient HE4 results should be used in conjunction with other clinical methods for monitoring ovarian cancer.
The use of this test in disease states other than ovarian cancer has not been clinically validated.
Serum markers are not specific for malignancy and values may vary by method. Values obtained with different assay methods cannot be used interchangeably. Correlation studies between this method and the previous enzyme-linked immunosorbent assay method show good correlation (correlation coefficient =0.92). However, this method will, on average, give 28% higher HE4 concentrations and individual patient results may vary more than would be calculated from the correlation equation.
Ideally, when changing methods, parallel testing using the old and new method allows for establishing the patient's HE4 baseline levels with the new method (rebaseline).
In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can rarely occur and may also interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.
Method Description
The Roche Elecsys HE4 (human epididymal protein 4) assay is a sandwich electrochemiluminescence immunoassay that employs a biotinylated monoclonal HE4-specific antibody and a monoclonal HE4-specific antibody labeled with ruthenium complex. HE4 in the specimen reacts with both the biotinylated monoclonal HE4-specific antibody (mouse) and the monoclonal HE4-specific antibody (mouse) labeled with ruthenium, forming a sandwich complex. Streptavidin-coated microparticles are added and the mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed. Application of voltage to the electrode induces the chemiluminescent emission, which is then measured against a calibration curve to determine the amount of HE4 in the patient specimen.(Package insert: Roche Elecsys HE4. Roche Diagnostics; V 3.0, 06/2024)