Test Catalog

Test Id : HE4

Human Epididymis Protein 4, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

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.

Method Name
A short description of the method used to perform the test

Electrochemiluminescence Immunoassay

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

HE4, S

Aliases
Lists additional common names for a test, as an aid in searching

WFDC2

HE4

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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: Aliquot Tube, 5 mL (T465)

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.

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.75 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 84 days
Refrigerated 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Females: < or =140 pmol/L

Males: Not applicable

Interpretation
Provides information to assist in interpretation of the test results

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
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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

Method Description
Describes how the test is performed and provides a method-specific reference

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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Saturday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

3 Months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86305

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports