Slightly elevated HE4 – diagnostic value

Ovarian cancer is asymptomatic. When the symptoms associated with the disease begin to appear, we are dealing with a neglected cancer process, which significantly reduces the chances of a complete cure. Currently, diagnostic methods are available, thanks to which it is possible to identify the disease at an early stage of its development, when treatment brings the best results. Unfortunately, many women still avoid preventive examinations and do not know what symptoms may indicate ovarian cancer.

The number of diagnosed cases of ovarian cancer is increasing every year. Among all female oncological diseases, a malignant ovarian tumor is characterized by an aggressive course and the highest mortality among all oncological diseases of the female reproductive system.

Women in their 40s and 50s are most commonly affected, although younger and older women and even children can develop this cancer. Average age is one of the risk factors for the disease, which is high in perimenopausal and postmenopausal women. Every woman should regularly visit a gynecologist and undergo the necessary preventive examinations. More frequent visits to the doctor are recommended for perimenopausal and menopausal women with close relatives diagnosed with ovarian cancer, breast cancer, and endometrial cancer.

In ovarian cancer, it is very important to study tumor markers, since in some patients in the early stages of the disease, the results of ultrasound looked quite typical. Measurement of tumor markers is currently not a problem. The medical laboratories of most clinics measure the HE4 marker and other tumor markers, as well as the ROMA (Risk of Ovarian Malignancy Algorithm) test, which allows you to determine whether the detected tumor can be malignant. The tests can be performed either with National Health Fund funds or for a fee, and are not expensive.

1. Ovarian cancer in numbers

Ovarian cancer accounts for 5% of all cancers in women. Although it may seem insignificant, the incidence of ovarian cancer in Poland is several percent higher than in other European countries. The same applies to the 5-year survival rate, which has dropped by as much as 8 points in recent years. Among young women, ovarian cancer is responsible for 9% of cancer deaths.

Approximately 4,000 new cases of ovarian cancer are diagnosed each year in women of all ages. In most cases, these are late-stage tumors that have metastasized to other abdominal organs. Recently, the HE4 tumor marker has been used in the diagnosis of ovarian cancer, the measurement of which makes it possible to detect the disease in the early stages of development. The HE4 marker is one of the tests that every woman should perform when the results of an ultrasound or gynecological examination indicate changes in the ovaries.

2. What tumors can form in the ovaries?

Not every lesion of the left or right ovary is a malignant tumor. Benign lesions are also very common in the ovaries. Some of them do not require specialized treatment, but only observation and, for example, the use of pharmaceuticals. Only some ovarian tumors require surgical treatment. Common changes in the ovaries include: ovarian cysts. Some lesions on the ovaries are hormonal, meaning that they produce hormones that further disrupt the body’s functioning.

Ovarian cancer is a very complex type of cancer that is difficult to diagnose and treat. As already mentioned, most often it is detected at an advanced stage of development, which significantly reduces the chance of a complete cure. The absence of characteristic symptoms of the disease is also a problem. Ovarian cancer may not cause symptoms for a long time. Ailments can appear only when the tumor compresses the surrounding structures or causes metastases to other organs. Warning symptoms that may indicate ovarian cancer include:

• an increase in the circumference of the abdomen,

• pain or periodic stabbing pains in the ovaries and throughout the lower abdomen,

• change in the frequency of urination,

• constipation,

• bloating,

• quick feeling of satiety after eating

• feeling of pressure in the abdomen

• sensation of the presence of a foreign body in the abdominal cavity,

• bleeding or spotting between periods.

Ovarian cancer can be inherited. The risk of its occurrence increases in the case of mutations in the BRCA1 and BRCA2 genes. Most cases of ovarian cancer are diagnosed in women entering the perimenopausal period, ie. in women aged 40-50 years, as well as in women who have experienced menopause. The risk of developing the disease is slightly reduced in women over 70 years of age.

3. Significance of HE4 (human epidymal protein 4) in the diagnosis of ovarian cancer.

HE4 is a new marker that helps detect ovarian cancer. The test is carried out together with the measurement of the marker CA-125. The HE4 antigen belongs to a subgroup of proteins derived from the epithelial cells of the epididymis. The HE4 and CA-125 tests allow you to perform the ROMA test (Ovarian Cancer Risk Algorithm). This test plays an important role both in the diagnosis of cancer in the late stages (III and IV) and in the early stages of development (I and II). An increased concentration of the HE4 protein is observed, i.e. in patients with other malignant neoplasms of the reproductive system, incl. endometrial cancer.

A slightly elevated HE4 marker does not always indicate ovarian cancer, since it is also secreted by healthy tissues. However, an elevated HE4 marker is always an indication for additional tests aimed at identifying the true cause of the presence of this protein in the blood. In the case of elevated HE4, the final confirmation of the doctor’s suspicions is the histopathological result, which allows a clear answer to the question: what change in the ovary are we dealing with?

The ROMA algorithm makes it possible to assign patients with ovarian lesions to the risk group of malignant neoplasm with high reliability. It is worth knowing that both cancerous and non-cancerous changes in the ovaries are diagnosed in women of all ages, constituting a serious gynecological problem. Most changes in the ovaries are benign and may disappear spontaneously or decrease under the influence of pharmacological treatment. Regular examinations by a gynecologist are the basis for the prevention of the health of the organs of the female reproductive system. It is worth remembering them and consulting a doctor about all the ailments that may indicate diseases of the ovaries and uterus.

4. What is the HE4 test?

The HE4 test is done after a blood sample has been taken. To determine the level of the HE4 protein, enzyme immunoassays are used, thanks to which the HE4 marker in the blood serum can be measured.

You need to properly prepare for the test. Correct behavior before the test is very important, as it helps to avoid falsifying the results.

The HE4 marker is determined in fasting blood. Women whose health condition is not a contraindication are allowed to participate in the study. Proceed before the HE4 test in the same way as before any other laboratory test. The test should not be performed in the presence of symptoms of seasonal infections, such as low-grade fever or fever, runny nose, cough, etc. In addition, a few days before the test, the woman should follow a healthy diet, avoid stimulants and stress. . Excessive exercise is also not recommended. Fatigue of the body with work at night or insomnia, as well as taking certain drugs, for example. vitamin H (biotin). Before the study, it is worth discussing with the gynecologist important issues that will avoid falsifying the result of measuring the HE4 marker.

5. When should the HE4 test be done?

Determination of the HE4 tumor marker is important when an ovarian lesion is detected on ultrasound, the nature of which may indicate ovarian cancer. It is worth knowing that the results of ultrasound are not always enough to determine what kind of lesion we are dealing with. It happens that the picture of the lesion is nonspecific and then it is necessary to take the drug for histopathological examination.

A broader diagnosis includes not only determining the level of HE4, but also performing a ROMA test. Simultaneous determination of HE4 and CA-125 markers makes it possible to assess the likelihood of developing malignant ovarian cancer in this patient. The combined determination of oncomarkers typical for ovarian cancer and the ROMA test is currently an increasingly used diagnostic method that significantly increases the detection of ovarian cancer at an early stage of its development by ultrasound results and determination of the level of CA-125 in blood serum. do not always indicate a serious illness. Elevated levels of the HE4 marker in the blood serum occur in more than 50% of all cases of clear cell ovarian cancer and in approximately 85-90% of cases of serous and endometrial cancers, which are among the most commonly diagnosed ovarian tumors.

It happens that the level of HE4 exceeds the established norms in other oncological diseases, which include m. colorectal cancer, pancreatic cancer, endometrial cancer and lung cancer.

6. Summary

Slightly elevated HE4 is not always associated with cancer, since this protein is also secreted by healthy tissues. In ovarian cancer, which is characterized by high mortality in women of all age groups, it is recommended to determine the level of HE4 in conjunction with the CA-125 marker test and the ROMA test, which allows to determine the risk of developing malignant ovarian cancer. . The HE4 test should be performed when changes are detected in the ovary that may indicate a malignant tumor.