Abstract
Women with endometriosis are at increased risk of developing ovarian cancer, specifically ovarian endometrioid, low-grade serous, and clear-cell adenocarcinoma. An important clinical caveat to the association of endometriosis with ovarian cancer is the improved prognosis for women with endometriosis at time of ovarian cancer staging. Whether endometriosis-associated ovarian cancers develop from the molecular transformation of endometriosis or develop because of the endometriotic tumor microenvironment remain unknown. Additionally, how the presence of endometriosis improves prognosis is also undefined, but likely relies on the endometriotic microenvironment. The unique tumor microenvironment of endometriosis is composed of epithelial, stromal, and immune cells, which adapt to survive in hypoxic conditions with high levels of iron, estrogen, and inflammatory cytokines and chemokines. Understanding the unique molecular features of the endometriotic tumor microenvironment may lead to impactful precision therapies and/or modalities for prevention. A challenge to this important study is the rarity of well-characterized clinical samples and the limited model systems. In this review, we will describe the unique molecular features of endometriosis-associated ovarian cancers, the endometriotic tumor microenvironment, and available model systems for endometriosis-associated ovarian cancers. Continued research on these unique ovarian cancers may lead to improved prevention and treatment options.
Highlights
Endometriosis is a debilitating disease that is estimated to affect up to 5 million U.S women and girls
The presence of endometriosis increases the risk of ovarian endometrioid, low-grade serous, and clear-cell adenocarcinoma by up to 8.9-fold but not high-grade serous adenocarcinoma [7,8,9,10,11,12]
Studies suggest that co-occurrence of endometriosis with ovarian cancer is associated with an improved prognosis [17,18,19,20]
Summary
Endometriosis is a debilitating disease that is estimated to affect up to 5 million U.S women and girls. Ovarian endometrioid, low-grade serous, and clear-cell adenocarcinomas are considered endometriosis-associated ovarian cancers. 5 million U.S women and girls with endometriosis are at risk for developing deadly ovarian cancer. Studies suggest that co-occurrence of endometriosis with ovarian cancer is associated with an improved prognosis [17,18,19,20]. Important factors in this improved prognosis include discovery at early age and early stage disease in women with endometriosis at time of ovarian cancer staging [21,22,23,24], but may Cancers 2018, 10, 261; doi:10.3390/cancers10080261 www.mdpi.com/journal/cancers. This review will focus on the contributions of the endometriotic tumor microenvironment to ovarian cancer biology
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