Tumor marker HE4
Why this test?
For diagnosis, assessment of prognosis and tumors treatment control of the ovary and endometrium.
In what cases is it prescribed?
If ovarian or endometrial cancer is suspected.
HE4 (from the English Human epididymis protein 4) is a small protein (molecular weight 25 kD) that belongs to the family of proteins that contain 4 disulfide bonds.
Initially, it was found in the distal epithelium of the epididymal duct (epididymal duct), hence the name human epididymal protein. Subsequently, it became known that HE4 is also produced in many other tissues (glandular epithelium of the mammary gland, female and male reproductive systems, distal renal tubules, colon, salivary glands). The physiological role of HE4 has not been fully elucidated, it is probably necessary for the normal functioning of the epithelium. In addition, it supports the innate immune system of the respiratory tract and oral cavity.
Enhanced synthesis of HE4 is characteristic of some malignant tumors (mesothelioma, lung cancer, kidney, breast cancer, endometrium, malignant formations of the gastrointestinal tract), which allows the use of this protein as a tumor marker. HE4 has been shown to have properties that promote tumor progression, for example, it enhances the migration and adhesion of ovarian cancer cells. HE4 is most important in the diagnosis, assessment of the prognosis and control of the treatment of tumors of the ovary and endometrium
One of the most difficult diagnostic tasks is the differential diagnosis of benign and malignant tumors of the pelvis. CA-125 tumor marker is often used for this. A significant disadvantage of CA-125 is its lack of specificity, as it can be elevated even in benign diseases. Compared with CA-125, the tumor marker HE4 is less often elevated in benign neoplasms (in 8% of cases versus 29%). CA 125 is also elevated in 67% of endometriosis cases, while HE4 is only elevated in 3%. Thus, the advantage of HE4 is a higher specificity for malignant formations.
When using a combination of tumor markers CA 125 and HE4, it is possible to differentiate malignant and benign tumors of the small pelvis more accurately than when using each marker separately. The combination of these tumor markers in combination with the patient's menopausal status is used in the ROMA ovarian cancer risk calculation algorithm.
To date, there is no test or method that would effectively detect ovarian cancer at an early stage. CA 125 is most often used for these purposes. This tumor marker, however, is not very sensitive and is detected only in 30-50% of ovarian cancer in the early stages. It has been shown that HE4 can be detected in 32% of CA 125-negative ovarian cancers and therefore complements CA 125.
HE4 is included in most panels of tests that are proposed to be used for ovarian cancer screening. The best result is shown when using a combination of HE4, CA-125, carcinoembryonic antigen CEA and vascular endothelial adhesion molecule type 1 VCAM-1: the combination of these tumor markers detects ovarian cancer in the early stages with a sensitivity of 86% and a specificity of 98%.
It is important to emphasize that the tumor marker HE4, as well as the tumor marker CA-125, is able to detect only ovarian malignant formations of epithelial origin and does not detect germinogenic tumors or tumors of the stroma of the genital tract.
Some studies have also shown that HE4 can be used to screen for endometrial cancer.
An increased level of HE4 is associated with a higher degree of malignancy and a more pronounced stage of ovarian cancer according to the FIGO classification. A high level of HE4 is more often observed in more aggressive variants of ovarian cancer and indicates a less favorable prognosis.
As with ovarian cancer, elevated HE4 levels are associated with a more aggressive endometrial cancer phenotype, and high concentrations of this tumor marker indicate a poor prognosis.
The study on HE4 can be used to evaluate the effectiveness of treatment. Thus, the concentration of HE4 is significantly different in patients diagnosed with ovarian cancer and patients who have achieved complete clinical remission (324.1 vs. 23.3 picomoles).
The HE4 test can also be used to diagnose ovarian cancer recurrence. It is shown that HE4 begins to be determined approximately 4.5 months before the appearance of clinical signs of relapse of this disease. On this basis, HE4 analysis is used to monitor the effectiveness of treatment. In some cases, an increase in HE4 precedes an increase in CA-125. In one of the studies, it was shown that the tumor marker HE4 is able to detect the recurrence of ovarian cancer with a sensitivity of 74% and a specificity of 100% at a concentration of more than 70 picomoles / l. The use of a combination of tumor markers HE4 and CA-125 allows to increase the sensitivity to 76%.
An increased level of HE4 is detected in 80% of cases of recurrence of endometrial cancer. It has been shown that the HE4 tumor marker is capable of detecting endometrial cancer recurrence with a sensitivity of 81% and a specificity of 64% at a concentration of more than 70 picomoles/L.
When interpreting results of the study, it should be remembered that HE4 can be increased in some other diseases, including lung cancer, renal failure and renal fibrosis. With age, the normal concentration of HE4 increases significantly (in contrast to CA-125, which normally decreases with age)