Oncological aspects of ovarian endometriosis

Abstract

Ovarian cancer is the second most common cause of death from gynaecological malignancies in the world, and in Ukraine it is the most serious type of gynecological cancer. Ovarian endometriomas significantly increase the risk of ovarian cancer, but their malignant transformation occurs in approximately 1% of cases.The article presents a literature review based on the scientific databases PubMed and Scopus for 2013–2023 on the incidence and frequency of ovarian malignant tumors on the background of ovarian endometriosis, carcinogenic mutations, immunological and hormonal disorders in ovarian endometriosis, which can cause its progression to ovarian cancer.Based on the analyzed scientific data, the connection between ovarian endometriosis and ovarian cancer is presented and all possible pathogenetic pathways through which ovarian endometriosis can lead to the formation of ovarian cancer are determined.According to the scientific literature, ovarian endometriosis can indeed lead to the formation of endometrioid and clear cell carcinomas, as well as other subtypes of malignant ovarian tumors. The risk of malignant changes in patients with ovarian endometriomas increases with age, the highest risk is observed in patients over 50 years of age. Despite this, some researchers believe that there are no time limits in the occurrence of malignant transformation of endometrioid ovarian cysts.Today, it is believed that atypical ovarian endometriosis, which is characterized by cytological atypia and architectural proliferation, is a precursor to ovarian cancer, and this condition that has the greatest risk for malignant process development is observed. Ovarian endometriomas contain a huge amount of heme and free iron, which leads to the appearance of an excess of free iron, and as a result, redox disorders occur, which cause carcinogenic mutations and destruction of cellular structures.Mutations in such genes as ARID1A, PIK3CA, AKT1, ERBB2 and PIK3R1, CTNNB1, KRAS, BRAF, PPP2R1A and occasionally in TP53 gene are involved in the occurrence of malignant changes in ovarian endometriomas. The same mutations are found in endometrioid foci of the ovaries and in endometrioid and clear cell carcinomas, which confirms the cancer development due to endometriosis. Disorders in the immune system in endometrioid lesions of the ovaries play a significant role in possible malignant transformation. The production of tumor necrosis factor, interleukin-1β, interleukin-6 increases, the function of natural killers decreases, and immunosuppression increases.Ovarian endometrioid cysts overexpress estradiol because they have increased amounts of the enzyme aromatase and lack the enzyme 17β-hydroxysteroid dehydrogenase type II, which is required to convert estradiol to estrone. Such changes lead to increased proliferative processes, which can also lead to the activation of oncogenic mutations.Thus, ovarian endometriosis significantly increases the risk of developing ovarian cancer, especially endometrioid and clear cell carcinomas. The mechanism of malignant transformation occurs precisely with the appearance of atypical endometriosis of the ovaries. The main pathogenetic pathways through which a malignant process can develop in ovarian endometriomas include: redox imbalance, which triggers a whole spectrum of oncogenic mutations, as well as immune disorders and exposure to high levels of estrogens. However, if patients with ovarian endometriomas are properly managed, the likelihood of ovarian cancer development is low.