1. Pathology and tumour markers
  2. Gold standard for diagnosis: CA-125
  3. New markers: HE4
  4. The combination of the two: R.O.M.A algorithm

Pathology and tumour markers

Ovarian carcinoma is one of the most common forms of neoplasia of the female reproductive system. The survival rate is inversely proportional to the stage of the illness at the time of diagnosis, so for this reason, to ensure a better prognosis, it is really important to get an early diagnosis for those women with suspicious symptomatology.

Gold standard for diagnosis: CA-125

Epithelial ovarian cancer (EOC) is diagnosed by laboratory tests, through the quantitative determination of the CA-125 (Cancer Antigen 125) marker. However the use of this marker alone as a screening test is not recommended for its low specificity and also because its levels increase in case of benign diseases such as endometriosis and uterine fibroids. CA-125 is considered the “gold standard” for monitoring those patients with ovarian cancer that have already undergone surgery because an increase in its levels after surgery is predictive of recurrence of the disease. To increase diagnosis specificity for this pathology, other markers have been introduced.

New markers: HE4

Among these there is the Human Epididymis Protein HE4 that is one of the most promising ones. This protein has initially been identified in the epithelium of the distal epididymis (testicle) as a protease inhibitor, with protease being an enzyme involved in the production of spermatozoa. The importance of this marker is due to the fact that the expression of the protein in normal conditions is restricted to the reproductive system and to the respiratory epithelium while it is hyper-expressed in epithelial ovarian cancer. HE4 levels in healthy women increase normally and gradually with age and menopause. Differently from CA-125, the HE4 marker has proved to have a 96% specificity and an 80% sensitivity because its levels do not increase in case of benign pathologies such as ovarian cysts. However its levels can increase in case of other neoplasms like pancreas or breast cancer. In addition, HE4 has proved to be more sensitive compared to the CA-125 marker in patients with ovarian cancer even in the early stages of the illness. To date, the better sensitivity and high specificity of the HE4 marker allows the differentiation of benign and malignant ovarian cysts, ovarian cancer and endometriosis.

The combination of the two: R.O.M.A algorithm

Several studies have shown that the combination of HE4 and CA-125 has a greater sensitivity and specificity compared to the markers being individually evaluated. This has suggested the use of a calculation algorithm known as R.O.M.A (Risk of Ovarian Malignancy Algorithm) that, combining the results of HE4 and CA-125, expresses an objective and quantitative index that shows the risk of malignant ovarian cancer. Therefore the ROMA algorithm allows to address patients to in-depth diagnostic analysis. In addition, such combination helps in obtaining a better specificity in the screening and diagnosis phases and represents a prognosis index as well as a therapeutic monitoring index for those patients undergoing chemotherapy treatment.

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