New insights into pattern recognition receptors and their ligands in gynecologic pathologies

In the ovary, clear cell carcinoma (CCC) and endometrioid adenocarcinoma occur in the setting of endometriosis. In this review, we discuss the role of innate immune responses, specifically endogenous ligands (also known as “alarmins”), their pattern recognition receptors (PRRs) and their signaling pathways, in the pathogenesis of ovarian cancer, in particular, endometriosis-associated ovarian cancer. This article reviews the English-language literature for pathogenesis and pathophysiological studies on endometriosis and ovarian cancer. Here, we show that iron functions as an endogenous ligand and can induce chromosomal instability through production of reactive oxygen intermediates-induced oxidative stress. Several important CCC-related genes overlap with those known to be associated with hepatocyte nuclear factor–1β–dependent oxidative stress. Aberrant expression of PRRs and HNF-1β in endometriosis has been reported in the setting of chronic inflammation and oxidative stress pathways, which lie downstream of these genes. A concerted overexpression of alarmins, their receptors and HNF-1β might be required for endometriosis carcinogenesis. Recent advances in innate immunity illuminate the molecular mechanism underlying inflammation-induced carcinogenesis. Upregulation of PRRs expression may synergize with activation of HNF-1β signaling to accelerate endometriosis proliferation and cause carcinogenesis.