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Tumor markers for ovarian cancer

Tumor markers for ovarian cancer are very important and the most known once are CA-125 and HE4. Scientists tested several markers and few combinations of tumor markers and they noted that the combination of two markers CA-125 and HE4 can be considered as the best diagnostic test for epithelial ovarian tumors. At the same time, it was noted that ovarian germ cell tumors and mucinous ovarian tumors rare can be detected by HE4. This is why HE4 cannot be considered as the accurate test for mentioned two types of ovarian cancer.

About 30% of all female reproductive system tumors are detected in ovaries and every fourth woman die from ovarian cancer (among all malignant diseases). Ovarian cancer mortality rate in Europe is 3,6-9,3 per 100 000 women.

Sometimes women could have different types of abdominal tumor (malignant or benign) and it is absolutely crucial to make the differentiation between benign and cancerous cells. According to medical statistics, in USA about 5-10% women experience abdominal surgery for ovarian cancer but only 13-21% of these women received histological confirmation of malignant tumors – actually only in some cases ovarian cancer was detected. As the methodology of surgery and the volume of surgery depend of correct diagnosis, it is very important to detect malignant tumors before operation.

Since most tumors detected in the pelvic cavity are benign, it is very important to assess the risk of surgery beforehand. Early diagnosis is crucial for better prognosis and higher survival rates (especially in cases with ovarian cancer). The survival rate of ovarian cancer depends on the stage of the disease. For example, the five-year survival of stage I ovarian cancer is 85-90% but unfortunately the survival rate is less than 20% in cases of late detection.
Sometimes ovarian cancer called “silent killer” because at early stages women cannot feel any warning symptoms or symptoms are not specific. This is why in 75% cases the epithelial ovarian tumors are detected at stages III or IV. And this is why the tumor markers for ovarian cancer should be used more widely.

Tumor markers for ovarian cancer

Tumor markers for ovarian cancer

Most popular tests for ovarian cancer detection are pelvic exam, ultrasound and tumor marker CA-125. In advanced clinics computed tomography (CT) and magnetic resonance imaging (MRI) are also routine tests for ovarian cancer.
Tumor markers for ovarian cancer are important. The most important marker is CA-125 which is able to detect ovarian cancer in 80% cases. Unfortunately the level of CA-125 can be “normal” in most cases of I and II stages of ovarian cancer. Only in 50% women with I and II stages of ovarian cancer doctors could discover increased levels of CA-125. In addition, the CA-125 is not strictly specific marker for ovarian cancer – it may be elevated in benign gynecological diseases, endometriosis, inflammation, other types of cancer, in healthy pregnant women (during first trimester of pregnancy).

According to American scientists, the CA-125 sensitivity in cases of I stage of ovarian cancer is about 7.1 to 19.7%. The sensitivity of CA-125 during next stages of ovarian cancer can be different – ranged from 23.2% to 59.4%.

In order to improve the diagnostic value of laboratory tests it has been studied the possibility of using the combined use of CA-125, and other tumor markers. The best results were obtained by joint use of CA-125 and HE- 4. It should be mentioned that HE-4 is a specific protein – Human Epididymis protein 4 (HE4) belongs to the family of whey acidic four-disulfide core proteins. First detected on cells in the epididymis where the HE-4 is involved in maturation of sperm. It is possible that HE-4 also has antimicrobial and anti-inflammatory activities.
HE- 4 can be determined in small amounts in the epithelia of the reproductive organs, upper respiratory tract and pancreas. Increased production of HE-4 occurs in ovarian cancer and endometrial cancer. In rare cases levels of HE-4 can be increases during common forms of lung adenocarcinoma.

According to recent studies, in the normal ovarian tissue there is minimal expression of the gene encoding the HE-4 – this is why in women with benign ovarian cysts and endometriosis the increased levels of HE-4 do not occur. Only in cases of cancerous ovarian transformation levels of HE-4 start increasing.

Normal level of HE-4 in blood: premenopausal – up to 70 nmol / l; postmenopause – up to 140 pmol / l.

It was noted that in about 1/3 women with ovarian cancer the level of CA-125 remains normal, while the level of HE-4 is increased. Scientists have proved the high sensitivity of tumor marker HE-4 during early stages of ovarian cancer, when there are no symptoms and the results of other tests (ultrasound, laboratory blood tests, etc.) are normal. Increased levels of HE-4 can be detected 3 years before medical diagnosis and increased levels of CA-125 could be detected 8-10 months before final diagnosis. This is why special attention should be paid to tumor markers for ovarian cancer.

Nowadays the simultaneous testing of the blood levels of ovarian tumor markers CA 125 and HE-4 has the highest sensitivity (76%) and specificity (95%). It is the best diagnostic test for early detection of ovarian cancer (for present time). Future scientific studies hopefully will provide better diagnostic tests for ovarian cancer.


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