Abstract
Endometriosis is a benign gynecological disease that affects women of reproductive age. Although malignant transformation of endometriosis is rare, physicians must be aware of this due to the high incidence of clear cell carcinoma of the ovary (CCC) in Japan. The most prevalent histological subtype of ovarian cancer is CCC (~70%) followed by endometrioid carcinoma (30%). The present review discusses the clinicopathological and molecular features of endometriosis-associated ovarian cancer (EAOC) as well as prospects for novel diagnostic strategies. Papers published between 2000 and 2022 in the PubMed and Google Scholar databases were included. Contents of the endometriotic cyst fluid may be involved in carcinogenesis, although the underlying mechanisms are largely unknown. Some studies have proposed a possible mechanism wherein excessive hemoglobin, heme and iron could cause an imbalance in intracellular redox homeostasis in endometriotic cells. Combined with DNA damage and mutations, the imbalances may induce the development of EAOC. Endometriotic cells evolve to adapt to the prolonged unfavorable oxidative microenvironmental stress. On the other hand, macrophages enhance the antioxidative defense mechanism and protect endometriotic cells against oxidative damage through intercellular crosstalk and signaling pathways. Therefore, changes in redox signaling, energy metabolism and the tumor immune microenvironment could be the key elements in the malignant transformation of certain endometriotic cell clones. Additionally, non-invasive bioimaging (i.e., magnetic resonance relaxometry) and biomarkers (i.e., tissue factor pathway inhibitor 2) may be promising tools for early-stage detection of the disease. In conclusion, the present review summarizes the latest advancements in research on the biological characteristics and early diagnosis of malignant transformation of endometriosis.