Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy

Abstract

Endometrial cysts (ECs) are thought to be the origin of endometriosis-associated ovarian cancer (EAOC). A hypothesis that the oxidative stress of iron in cysts causes “malignant transformation of ECs” has been proposed, but this has not been verified. Several population-based studies showed that endometriosis was a risk factor but did not reflect the “malignant transformation of ECs”. A review showed that most patients were diagnosed with EAOC early in monitoring following detection of ECs, and that these cases might have been cancer from the start. Epidemiologically, EAOC was reduced by hysterectomy rather than by cystectomy of ECs. Gene mutation analyses identified oncogenic mutations in endometriosis and normal endometrium and revealed that the same mutations were present at different endometriotic lesions. It was also shown that most of the gene mutations found in endometriosis occurred in normal endometrium. Taking together, EAOC might be caused by eutopic endometrial glandular epithelial cells with oncogenic mutations that have undergone menstrual blood reflux and engrafted in the ovary, rather than by low-risk ECs acquiring oncogenic mutations and becoming malignant. This review discusses the mechanisms of EAOC development and targeted therapy based on genetic variation in EAOC with a focus on eutopic endometrium.

Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome

“…For example, in epidemiological studies it has been observed that tubal ligation, that usually blocks tubal lumen and passage, decreases the risk for ovarian cancer [ 42 , 43 ]. Also, endometriosis has been postulated as a risk factor for ovarian cancer [ 44 , 45 ]. Inflammation due to tubal endometriosis is a known factor involved in ovarian cancer carcinogenesis, mainly through DNA mutation mediated by free radicals associated with inflammatory process [ 46 ].…”

FrequentPIK3CAmutations in eutopic endometrium of patients with ovarian clear cell carcinoma

“…This study was conducted to examine our hypothesis that EAOC originates from eutopic endometrium [9] and determine whether eutopic endometrium has a high frequency of mutations identical to EAOC. However, the results obtained were quite different from our predictions.…”

“…Notably, a case of clonal lineage from eutopic endometrium to endometriosis and OCCC was reported [8]. Therefore, eutopic endometrium has recently attracted a great deal of interest as a potential origin of EAOC [9]. A previous study showed that endometrial glands are composed of monoclonal cell populations [10].…”

Polyphenols as a Diet Therapy Concept for Endometriosis—Current Opinion and Future Perspectives

“…It affects approximately 10–15% of women of reproductive age, which extrapolates to around 190 million women worldwide [ 1 , 2 ]. Most affected patients often suffer from chronic pelvic pain, dyspareunia, dysmenorrhea, abnormal uterine bleeding, and infertility [ 3 , 4 ]. All these symptoms provide an impact on a patient’s quality of life, resulting in depression, anxiety, and impaired social function caused by the severity of pain [ 5 ].…”