Human Epididymis Protein 4 (HE4)
- Also Known As:
- HE4

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.At a Glance
Why Get Tested?
To help monitor epithelial ovarian cancer after treatment; to detect recurrence or disease progression; not recommended for screening asymptomatic women for ovarian cancer
When To Get Tested?
Before starting therapy for epithelial ovarian cancer and at intervals after treatment
Sample Required?
A blood sample drawn from a vein in your arm
Test Preparation Needed?
None
You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Testing.com. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.
Testing.com is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.
The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.
If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.
Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.
While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”
For more information, please read the article Reference Ranges and What They Mean.
What is being tested?
Human epididymis protein 4 (HE4) is a protein that is produced by most, but not all, epithelial ovarian cancer cells. This makes the test useful as a tumor marker in specific circumstances. The HE4 test measures the amount of human epididymis protein 4 in the blood.
Significantly elevated concentrations of HE4 are frequently present in the blood of a woman who has epithelial ovarian cancer. When HE4 is increased, the HE4 test may be used to monitor the effectiveness of treatment and/or for recurrence or progression of the cancer.
Ovarian cancer is the fifth most common cause of cancer death in women. According to the American Cancer Society (ACS), the lifetime risk of a woman developing ovarian cancer is about 1 in 75 and the lifetime risk of death is 1 in 100. ACS estimates that about 22,000 new cases are diagnosed each year in the U.S. and about 14,000 women die of it.
Epithelial ovarian cancer is the most common type of ovarian cancer. It originates in cells that cover the outside of the ovaries and accounts for 85% to 90% of ovarian cancers.
There are several different subtypes of epithelial ovarian cancer, including: serous, endometrioid, mucinous, and clear cell, with serous being the most common. Some studies have shown that HE4 is elevated in more than 90% of serous and endometrioid epithelial ovarian cancers and about 50% of clear cell tumors, but it is not usually elevated in mucinous cancers. Therefore, HE4 is not used for monitoring of patients with other types of ovarian cancer, such as mucinous or germ cell tumors.
Currently, there is no reliable method for early detection of ovarian cancer among asymptomatic women. Less than 20% of ovarian cancers are found in the early stages before they have spread outside the ovary. One reason they go undetected is that the symptoms of ovarian cancer are fairly non-specific. The need for a reliable method for early detection of ovarian cancer among asymptomatic women continues to drive ongoing research. In the meantime, regular physicals, pelvic exams, and an awareness of family history and symptoms are important.
Common Questions
View Sources
Sources Used in Current Review
2020 review performed by Qing H. Meng PhD, MD, DABCC, FAACC, Professor and Director of Clinical Chemistry and Special Chemistry Laboratories, Department of Laboratory Medicine.
(April 11, 2018) American Cancer Society. Ovarian Cancer, Tests. Available online at https://www.cancer.org/cancer/ovarian-cancer.html. Accessed on 4/8/2020.
(April 2019) American College of Obstetricians and Gynecologists (ACOG). Ovarian Cancer, Frequently Asked Questions. Available online at https://www.acog.org/patient-resources/faqs/gynecologic-problems/ovarian-cancer. Accessed on 4/8/2020.
(April 2019) American Society of Clinical Oncology (ASCO). Ovarian, Fallopian Tube, and Peritoneal Cancer: Diagnosis. Available online at https://www.cancer.net/cancer-types/ovarian-fallopian-tube-and-peritoneal-cancer/diagnosis. Accessed 4/8/2020.
(August 19, 2019) Centers for Disease Control and Prevention. Ovarian Cancer. Available online at https://www.cdc.gov/cancer/ovarian/index.htm. Accessed on 4/8/2020.
Yang WL, Lu Z, Bast RC Jr. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn. 2017 Jun;17(6):577-591.
Sources Used in Previous Reviews
(2016 February 4 Revised). Ovarian Cancer, Detailed Guide. American Cancer Society [On-line information]. Available online at http://www.cancer.org/cancer/ovariancancer/detailedguide/index. Accessed on 03/04/16.
Ferraro, S. et. al. (2013). Serum Human Epididymis Protein 4 vs Carbohydrate Antigen 125 for Ovarian Cancer Diagnosis. Medscape Multispecialty from J Clin Pathol. 2013;66(4):273-281. [On-line information]. Available online at http://www.medscape.com/viewarticle/781857. Accessed on 03/04/16.
Hussain, F. et. al. (2015 January 13 Updated). Gynecologic Tumor Markers Tumor Marker Overview. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/269839-overview#a1. Accessed on 03/04/16.
(© 1995–2016). Human Epididymis Protein 4, Serum. Mayo Clinic Mayo Medical Laboratories. [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/62137. Accessed on 03/04/16.
Grenache, D. (2016 February Updated).Ovarian Cancer. ARUP Consult [On-line information]. Available online at https://arupconsult.com/node/2384. Accessed on 03/04/16.
Santotoribio, J. (2016 January 20). What are the tumor markers that best identify the epithelial ovarian cancer? NACB Scientific Shorts. [On-line information]. Available online at https://www.aacc.org/community/national-academy-of-clinical-biochemistry/scientific-shorts/2016/what-are-the-tumor-markers-that-best-identify-the-epithelial-ovarian-cancer. Accessed on 03/04/16.
(2015 November 4 Reviewed). Tumor Markers. National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet. Accessed on 03/04/16.
Jinping L. et. al. (2009). HE4 as a Biomarker for Ovarian and Endometrial Cancer Management. Medscape News & Perspective from Expert Rev Mol Diagn. 2009;9(6):555-566 [On-line information]. Available online at http://www.medscape.com/viewarticle/711023. Accessed on 03/04/16.
(2016 March 2). New Report Finds ‘Surprising Gaps’ in Knowledge of Ovarian Cancers; Better Understanding Needed to Make Progress in Prevention, Early Detection, Treatment, and Management of Disease. National Academies of Sciences, Engineering, and Medicine Press Release [On-line information]. Available online at http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=21841. Accessed on 03/04/16.
Algeciras-Schimnich, A. (2013 March 1). Ovarian Cancer, A Review of Current Serum Markers and Their Clinical Applications. Clinical Laboratory News [On-line information]. Available online at https://www.aacc.org/publications/cln/articles/2013/march/ovarian-cancer. Accessed on 03/04/16.
Zhuang, H. et. al. (2014 November 1). Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells. Molecular Cancer 2014 13:243. [On-line information]. Available online at http://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-243. Accessed on 03/04/16.
(2012 December Reviewed). HE4, Ovarian Cancer Monitoring. Quest Diagnostics [On-line information]. Available online at http://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_HE4_Ovarian_Cancer_Monitoring. Accessed on 03/04/16.
Chang, X. et. al. (2011 July). Human Epididymis Protein 4 (HE4) as a Serum Tumor Biomarker in Patients With Ovarian Carcinoma. Int J Gynecol Cancer. 2011; 21(5): 852-858. [On-line information]. Available online at http://journals.lww.com/ijgc/Abstract/2011/07000/Human_Epididymis_Protein_4__HE4__as_a_Serum_Tumor.12.aspx. Accessed on 03/04/16.
Macedo, A. et. al. (2014 September). Accuracy of serum human epididymis protein 4 in ovarian cancer diagnosis: a systematic review and meta-analysis. Int J Gynecol Cancer. 2014; 24(7):1222-31. [On-line information]. Available online at http://journals.lww.com/ijgc/Fulltext/2014/09000/Accuracy_of_Serum_Human_Epididymis_Protein_4_in.14.aspx#. Accessed on 03/04/16.
Drapkin, R. et. al. (2005). Human Epididymis Protein 4 (HE4) Is a Secreted Glycoprotein that Is Overexpressed by Serous and Endometrioid Ovarian Carcinomas. Cancer Res, March 15, 2005 65; 2162 [On-line information]. Available online at http://cancerres.aacrjournals.org/content/65/6/2162.full. Accessed on 03/04/16.
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