Human Epididymis Protein 4 (HE4) is a protein biomarker. Understanding its normal range in the blood is important for interpreting test results. This article explains what HE4 is, what its typical levels indicate, and the significance of results outside the expected range. It also covers factors that influence HE4 measurements.
What is HE4?
HE4, or Human Epididymis Protein 4, is a protein produced naturally by various body tissues. It is found in healthy tissues of the male reproductive system, particularly the epididymis, and in parts of the respiratory tract and nasopharynx.
HE4 is also present in various bodily fluids, including blood. While its exact biological function in healthy individuals is still under investigation, it is recognized for its presence in certain tumor cells. HE4 can be found in higher than normal amounts in individuals with some types of cancer, including epithelial ovarian cancer.
Understanding the Normal Range
The “normal range” for HE4 levels in the blood represents expected values in healthy individuals. Always refer to the specific reference range provided by the laboratory performing the test, as these can vary slightly. Generally, an upper limit of normal for serum HE4 is around 70 pmol/L.
The normal range for HE4 differs based on a woman’s menopausal status. For pre-menopausal women, a typical cut-off is around 60 pmol/L, while for post-menopausal women, a higher cut-off of approximately 170 pmol/L is common. This difference reflects physiological changes associated with menopause that can influence protein levels.
What Elevated HE4 Levels May Indicate
Elevated HE4 levels, meaning those above the established normal range, can suggest the presence of certain medical conditions. The primary clinical application for HE4 testing is in assessing the risk of epithelial ovarian cancer, particularly when used alongside another biomarker called CA-125. Combining HE4 and CA-125 measurements helps calculate a Risk of Ovarian Malignancy Algorithm (ROMA) score, which aids in classifying patients with a pelvic mass into high or low likelihood of malignancy.
HE4 has shown an ability to distinguish ovarian cancer from some benign gynecological conditions, such as endometriosis, where CA-125 levels might also be elevated. While its main utility is in ovarian cancer risk assessment and monitoring, elevated HE4 levels can also be associated with other conditions. These may include certain other cancers, such as endometrial, lung, or breast cancers, though less frequently than ovarian cancer. Kidney disease can also lead to increased HE4 levels due to impaired clearance from the body.
Important Considerations for HE4 Results
Several factors can influence HE4 levels beyond the specific conditions it is used to monitor. A person’s age, for instance, can affect HE4 concentrations, with levels tending to increase with advancing age. Certain non-cancerous medical conditions may also lead to elevated HE4 readings. It is important to consider a person’s overall health and medical history when interpreting these results.
HE4 testing is not a standalone diagnostic tool, nor is it a general screening test for the population. A single elevated HE4 result does not definitively diagnose cancer or any other condition. Instead, the results must always be interpreted by a healthcare professional, who will consider them in conjunction with other clinical information, such as physical examinations, imaging studies, and other blood tests. This comprehensive approach ensures an accurate assessment and guides any necessary further investigation or management.