Inflammation and the Malignant Transformation of Endometriosis
Abstract
Women with endometriosis have an increased risk of certain subtypes of ovarian cancer. Previous studies have reported that endometriosis tissue that is located directly next to ovarian cancer often has the same genetic mutations that are found in the ovarian cancer tissue. Some evidence suggests that one specific type of endometriosis, ovarian endometrioma, is the type of endometriosis that is most likely to become ovarian cancer. However, even when these type of endometriosis lesions are removed, some women still develop ovarian cancer. In addition, removing other types of endometriosis tissue has been shown to reduce risk of ovarian cancer. Further complicating our understanding of how endometriosis becomes ovarian cancer, a recent study found that ovarian cancer-related mutations were found in a type of endometriosis (deep infiltrating) that has not been thought to transition to ovarian cancer. These observations taken together indicate that there is much we do not know about what causes endometriosis lesions to progress to ovarian cancer. The critical problem that our research will address is that although we know endometriosis increases ovarian cancer risk, we do not know how to identify which women with endometriosis will develop ovarian cancer. Identifying a subset of high-risk women based on endometriosis tissue and peritoneal fluid characteristics, which can be collected when women have endometriosis surgery, has high potential to impact women with endometriosis as these women may substantially benefit from closer monitoring, more aggressive endometriosis treatment, or anti-inflammatory pharmacologic therapy. No previous studies have examined how peritoneal fluid influences the occurrence of cancer-driven mutations in endometriosis lesions and the growth potential of endometriosis lesions, thus examination of the peritoneal environment may create a new paradigm for how we assess the carcinogenic potential of endometriosis lesions. This project is directly related to the Fiscal Year 2018 (FY18) Peer Reviewed Medical Research Program (PRMRP) Topic Area of endometriosis, specifically the area of encouragement relating to elucidating the pathogenesis and evolution of endometriosis. Currently, women with endometriosis and their clinicians have little evidence to guide treatment decisions and to assess an individual woman’s risk of ovarian cancer based on endometriosis characteristics. This knowledge is important because the absolute risk of endometriosis progression to ovarian cancer is low, so the risk of ovarian cancer must be balanced with the risk of adverse outcomes from endometriosis surgeries and treatments. Thus, identifying women with endometriosis who are most likely to develop ovarian cancer is very important to lessen future ovarian cancer risk and minimize potential harm to the women with endometriosis who are unlikely to develop ovarian cancer. Our goal of identifying high-risk women is also relevant to the FY18 PRMRP area of encouragement to develop novel treatments to reduce secondary effects of endometriosis. Specifically, in the long term, it would provide us with us with information to help prevent the transformation of endometriosis to ovarian cancer through both detection of high-risk endometriosis lesions and the treatment of these lesions before they progress to ovarian cancer. Endometriosis affects approximately 10% of reproductive-aged women. Because endometriosis is a common condition, there may be a large impact on the health of military Service women and their female family members from the development of treatments and surveillance strategies that reduce the number of women with endometriosis that develop ovarian cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910128
Entities
People
- Holly R Harris
Organizations
- Fred Hutchinson Cancer Center
- United States Army