title: Models of endometriosis and their utility in studying progression to ovarian clear cell carcinoma.
abstract: Endometriosis is a common benign gynaecological condition affecting at least 10% of women of childbearing age and is characterized by pain--frequently debilitating. Although the exact prevalence is unknown, the economic burden is substantial (∼$50 billion a year in the USA alone) and it is associated with considerable morbidity. The development of endometriosis is inextricably linked to the process of menstruation and thus the models that best recapitulate the human disease are in menstruating non-human primates. However, the use of these animals is ethically challenging and very expensive. A variety of models in laboratory animals have been developed and the most recent are based on generating menstrual-like endometrial tissue that can be transferred to a recipient animal. These models are genetically manipulable and facilitate precise mechanistic studies. In addition, these models can be used to study malignant transformation in epithelial ovarian carcinoma. Epidemiological and molecular evidence indicates that endometriosis is the most plausible precursor of both clear cell and endometrioid ovarian cancer (OCCA and OEA, respectively). While this progression is rare, understanding the underlying mechanisms of transformation may offer new strategies for prevention and therapy. Our ability to pursue this is highly dependent on improved animal models but the current transgenic models, which genetically modify the ovarian surface epithelium and oviduct, are poor models of ectopic endometrial tissue. In this review we describe the various models of endometriosis and discuss how they may be applicable to developing our mechanistic understanding of OCCA and OEA.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: King
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, UK.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Barbara
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Prentice
authors.affiliation: Functional Genomics of Ovarian Cancer Laboratory, CR-UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, UK.|National Institute for Health Research, Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK.
authors.forename: James D
authors.initials: JD
authors.lastname: Brenton
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, UK.|National Institute for Health Research, Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK.
authors.forename: D Stephen
authors.initials: DS
authors.lastname: Charnock-Jones
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000209:etiology / Q000473:pathology*; D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000209:etiology / Q000473:pathology; D004715:Endometriosis / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008598:Menstruation / Q000502:physiology; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000209:etiology / Q000473:pathology*; D011323:Primates; D011817:Rabbits; D012377:Rodentia; D014183:Transplantation, Heterologous
keywords: animal model; clear cell ovarian cancer; endometrioid ovarian cancer; endometriosis; menstruation