Human Epididymis Protein 4, or HE4, is a protein biomarker that has become a valuable tool in the assessment of ovarian cancer. While it offers significant insights, it is not a standalone diagnostic and must be used as part of a broader clinical evaluation. This article explores what HE4 is, how its levels are measured, what the test results indicate, and its specific applications and limitations in managing ovarian cancer.
Understanding HE4
HE4, short for Human Epididymis Protein 4, is a protein naturally produced by certain cells within the human body. It is found in various tissues, including those of the reproductive tract, such as the fallopian tubes, endometrium, and ovaries.
In the context of ovarian cancer, HE4 is frequently overexpressed by malignant cells, particularly in the common epithelial types like serous and endometrioid ovarian carcinomas. Its elevated presence in the bloodstream of women with ovarian cancer makes it a useful biomarker. However, it is important to understand that HE4 is a marker of disease presence or activity, not a direct cause of cancer itself.
The HE4 Test: How and Why It’s Done
The HE4 test is a straightforward blood test that measures the amount of this protein circulating in the bloodstream. A healthcare professional typically obtains a blood sample from a vein in the arm, which is then sent to a laboratory for analysis. No specific preparation, such as fasting, is usually required before the test.
Doctors may order an HE4 test for several key reasons related to ovarian cancer management. These include monitoring treatment effectiveness and detecting recurrence in diagnosed patients. It is also used to help assess the risk of malignancy in women with a pelvic mass.
Interpreting HE4 Test Results
HE4 levels are typically reported in picomoles per liter (pmol/L). The interpretation of these results requires careful consideration, as normal ranges can vary based on a woman’s menopausal status and age. For instance, studies suggest that for healthy premenopausal women, the upper limit of the normal range for HE4 can be around 89 to 118.9 pmol/L, while for postmenopausal women, it may be higher, ranging from approximately 128 to 167.8 pmol/L. These values can also differ slightly depending on the specific laboratory and assay used.
An elevated HE4 level does not automatically confirm an ovarian cancer diagnosis. Other benign conditions, such as endometriosis, pelvic inflammatory disease, or even kidney issues, can sometimes lead to increased HE4 concentrations. Conversely, a normal HE4 level does not completely rule out the presence of ovarian cancer. Therefore, healthcare professionals always interpret HE4 results within the broader context of a patient’s medical history, physical examination findings, and other diagnostic tests, such as imaging studies.
HE4’s Role in Ovarian Cancer Management and Its Limitations
HE4 plays a specific role in the ongoing management of ovarian cancer, primarily after a diagnosis has been established. It is widely used to monitor how patients respond to treatment; a decrease in HE4 levels often suggests that the therapy is effective, while rising levels can indicate disease progression or recurrence. This marker can sometimes signal recurrence earlier than CA-125 alone. HE4 is also incorporated into risk assessment algorithms, such as the Risk of Ovarian Malignancy Algorithm (ROMA), which combines HE4 and CA-125 levels with a woman’s menopausal status to help predict the likelihood that a pelvic mass is malignant. This algorithm aids in directing patients to appropriate specialized care.
Despite its utility, HE4 has several limitations. It is not considered a screening tool for the general population due to its lack of absolute specificity and sensitivity for early detection in asymptomatic women. The biomarker is also less effective for certain rarer types of ovarian cancer, such as mucinous or germ cell tumors, as these may not produce elevated HE4 levels. This means a normal HE4 result in these cases would not be informative.