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Diagnosis of ovarian epithelial cancer by performing a HE4 test

Today, ovarian cancer is the second most common cancer in women and the fourth most common cause of cancer death.
The cancer, which has the highest mortality rate in women, is the most prevalent in industrial societies.
Global statistics show that out of more than 200,000 women with the disease, 140,000 of them die.

Epidemiology of ovarian epithelial cancer

 

Today, ovarian cancer is the second most common cancer in women and the fourth most common cause of cancer death. The cancer, which has the highest mortality rate in women, is the most prevalent in industrial societies.

Global statistics show that out of more than 200,000 women with the disease, 140,000 of them die.

Although treatments such as new drugs and surgeries have made great strides in recent years, the diagnosis is still difficult, especially in the early stages, which is an important step in treatment.

In many cases, the disease progresses and consequently reduces the patient's life expectancy, and unfortunately late diagnosis reduces the chances of treatment.

 

Early detection of ovarian epithelial cancer (EOC) * is still a major challenge in today's world. In 75% of patients with EOC, symptoms occur only in the later stages (Stage III, Iv), many of which include vague symptoms such as abdominal enlargement, abdominal pain, and frequent urination. The stage of the disease has progressed and will reduce the patient's life expectancy. 

The patient's life expectancy in EOC depends primarily on the timely diagnosis of the disease and then the type and quality of surgery to completely remove the tumor.

 

 

* EOC : Epithelial ovarian cancer

 

In the early stages, the disease has nonspecific symptoms, after which the patient may suffer from abdominal pain caused by so-called pelvic masses.

It is estimated that 5-10% of women who experience a pelvic mass during their lifetime undergo surgery for ovarian malignancy, of which about 13-21% have been reported. Therefore, new methods and biomarkers that can help diagnose ovarian cancer in the early stages are of great importance, in which the biomarker HE4 * along with CA125 can play a very important role in this regard.

 

HE4 and its diagnostic value in ovarian cancer:

HE4 was first identified in the distal epididymis. Thus, very high concentrations of HE4 were observed in the tissues and serum of patients with EOC. HE4, as a tumor marker, alone has the highest sensitivity in the diagnosis of ovarian cancer, especially in Stage-1 disease.

Unlike the normal superficial epithelium in the ovary, where HE4 is not expressed, protein is abundantly expressed in the cortical portion of the cyst by epithelial metaplasia. The level of this protein increases in all stages of EOC cancer, which is an important diagnostic marker, especially in the early stages of cancer compared to CA125, while a combination of HE4 and CA125 measurements can be used to accurately predict malignancy.

Therefore, measuring the HE4 marker is very helpful in assessing the risk of this cancer, as HE4 alone is recognized as an independent and important diagnostic marker in EOC cancer.

 

CA125 or HE4?

Estimation of early stages of ovarian cancer using only the CA125 marker provides limited diagnostic information, while adding more reliable and useful results can be achieved by adding a HE4 test.

Studies show that CA125 is increased in endometriosis, while HE4 is able to better distinguish between cancer and endometriosis. HE4 can also evaluate benign and malignant cases better than CA125. 

In general, measuring both biomarkers together can provide valuable information in differentiating ovarian malignancies from benign endometriosis cysts.

 

* HE4 : Human epididymal protein-4

 

It seems that the combination of HE4 and CA125 measurements is very important in predicting the outcome of appropriate surgery and the course of disease resistance in chemotherapy. HE4 helps CA125 better understand the status of ovarian cancer.

 

In addition to using HE4 and CA125 in risk classification in women with pelvic mass, HE4 can be used to control disease status in patients with EOC.

HE4 levels during initial chemotherapy are directly related to the patient's clinical and radiological responses. In neoadjuvant chemotherapy, HE4 levels show a better association with radiological responses than CA125. A change in an increase in HE4 concentration of more than 20% is considered a progression or recurrence of the disease, while a decrease in this rate is a sign of response to treatment.

 

► The combination of HE4 and CA125 in the detection of EOC has the highest sensitivity and value compared to other markers alone.

 

Recent studies comparing the value of measuring HE4 and CA125 at different stages of ovarian cancer suggest that:

- CA125 is an appropriate diagnostic marker for distinguishing negative cases of the disease as well as diagnosing its advanced stages.

- HE4 is not only a good distinguishing indicator of negative cases, but by measuring it, the disease can be diagnosed even in the early stages.

 

Today, HE4 measurement in patients' serum is used as a screening test for ovarian or endometrial cancer.

 

What is ROMA *?

It is an algorithmic index that uses the measurement of HE4 and CA125 markers by electrochemical luminescence method to estimate the risk of ovarian cancer in patients with pelvic mass. The ROMA calculation takes into account the patient's monoposal status and the final risk is reported by the laboratory.

 

* ROMA : Risk of ovarian malignancy algorithm

Date Release : 2021/06/28
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