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Epic Code LAB3087 Human Epididymis Protein 4, Serum

Additional Codes

Mayo Code: HE4

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Useful 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 or for monitoring patients with mucinous or germ cell ovarian cancer.

Specimen Type

Serum


Specimen Required


Patient Preparation: For 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Supplies: Sarstedt 5 mL Aliquot Tube (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 plastic vial.


Laboratory Test Directory Note:

COLLECTION NOTE: Volumes listed are in serum or plasma, draw approximately 2 1/2 times the requested volume in whole blood.

Specimen Minimum Volume

0.75 mL

Laboratory Test Directory Note:

COLLECTION NOTE: Volumes listed are in serum or plasma, draw approximately 2 1/2 times the requested volume in whole blood.

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

Day(s) Performed

Monday through Friday

Reference Values

Females: ≤140 pmol/L

Males: Not applicable

Clinical Information

Human epididymis protein 4 (HE4) belongs to the family of whey acidic four-disulfide core (WFDC) proteins. Currently, the biologic function of HE4 is unknown.

 

HE4 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 125 (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.

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 renal 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 ELISA 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, interference due to extremely high titers of antibodies to analyte-specific reagents (human anti-mouse or heterophile antibodies, streptavidin, or ruthenium) can occur. The laboratory should be alerted if the result does not correlate with the clinical presentation.

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.

Reporting Name

HE4, S

Method Name

Electrochemiluminescence Immunoassay

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. This method has been standardized against the HE4 EIA method from Fujirebio Diagnostics, Inc.(Package insert: Roche Elecsys HE4 reagent, Roche Diagnostics, V 1.0 English 01/2020)

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

Report Available

1 to 3 days

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

Clinical Reference

1. Moore RG, Brown AK, Miller MC, et al: The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008 Feb;108(2):402-408

2. Ferraro S, Braga F, Lanzoni M, et al: Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol. 2013 Apr;66(4):273-281