Endometriosis-Associated Ovarian Cancer: From Molecular Pathologies to Clinical Relevance Original paper

What was studied?

This review examines the molecular pathogenesis of endometriosis-associated ovarian cancer (EAOC), focusing on the genetic, epigenetic, and microenvironmental factors that contribute to the transformation of benign endometriotic lesions into malignancies. The study explores how endometriosis, a chronic condition where endometrial-like tissue grows outside the uterus, increases the risk of developing certain types of ovarian cancer, particularly endometrioid and clear-cell carcinoma. The article discusses the roles of various genetic mutations, including those in genes like p53, K-ras, ARID1A, PIK3CA, and PPP2R1A, as well as the influence of hormonal imbalances, oxidative stress, and inflammation in driving the progression of EAOC.

Who was studied?

The review focuses on molecular and clinical studies involving patients with endometriosis, specifically those at an increased risk for developing ovarian cancer. It explores the genetic and molecular profiles of ovarian endometriotic lesions and compares them with those of normal ovarian tissues and ovarian cancer. The article also highlights the tumor microenvironment, including factors like estrogen signaling, oxidative stress, and microRNA dysregulation, that may contribute to cancer progression in women with endometriosis. The study integrates findings from various patient cohorts and experimental models, emphasizing the need for personalized treatment strategies based on molecular signatures.

Most important findings

The study identifies several key molecular factors involved in the malignant transformation of endometriosis to ovarian cancer. Genetic mutations, such as in the p53 and K-ras genes, along with microsatellite instability, play a critical role in the initiation and progression of tumors. ARID1A mutations, which affect chromatin remodeling, are frequent in clear-cell and endometrioid ovarian carcinomas, leading to genomic instability and increased tumor aggressiveness. Additionally, mutations in the PIK3CA gene, which is involved in the PI3K/AKT/mTOR signaling pathway, were found to be early events in the development of EAOC, particularly in clear-cell carcinoma. The loss of ARID1A expression often coexists with these mutations, further complicating tumor progression. The review also highlights the role of estrogen in promoting endometriotic cell proliferation through signaling pathways, contributing to carcinogenesis. MicroRNAs, including miR-200 and let-7, are involved in regulating epithelial-to-mesenchymal transition and oncogenicity, making them potential biomarkers for EAOC. Moreover, the tumor microenvironment, shaped by oxidative stress and inflammation, further accelerates the carcinogenic process.

Key implications

The molecular insights provided by this review suggest that targeting specific genetic and molecular pathways could be an effective approach to treating EAOC. For example, inhibiting the PI3K/AKT/mTOR pathway, which is altered in many EAOC cases, or targeting microRNAs involved in tumor progression, could offer new therapeutic avenues. The review also emphasizes the importance of early detection, especially for patients with endometriosis who are at higher risk for developing ovarian cancer. Understanding the complex interplay between genetic mutations, hormonal factors, and the tumor microenvironment is crucial for developing more effective, personalized treatments for EAOC. Given the poor prognosis associated with clear-cell ovarian carcinoma, which is often diagnosed at advanced stages, the identification of specific molecular signatures could help tailor early interventions to improve patient outcomes.