The Role Of Implantation In Endosalpingiosis, Other Benign Gynecologic Lesions, And Ovarian Cancer

High grade serous carcinoma (HGSC) arises from the ectopic implantation of malignant oviductal epithelial cells (OECs) in the peritoneal cavity and on the ovarian surface (the “tubal origins hypothesis”). We believe that these cells hijack the process of implantation used by the blastocyst, to implant ectopically in the peritoneal cavity, and certain women inherently have a high implantation capability enabling a higher rate of ectopic implantation and a higher risk for HGSC and other benign lesions in parallel. Endosalpingiosis (ES) is the benign counterpart to HGSC as both originate from OECs. We and others have demonstrated that ES lesions are significantly associated with gynecologic malignancy among patients over 51 years of age. We therefore increased the scrutiny on benign appearing adnexal lesions to align with the Sectioning and Extensively Examining-Fimbria (SEE-Fim) protocol. The pathology database was then queried for the presence of ES, endometriosis (EM), walthard nests (WN), paratubal cysts (PTC), and gynecologic malignancy for a one year period prior to and after this practice change. Prior to introducing the SEE-Fim protocol the prevalence of ES was 3%, compared to 22% when using SEE-Fim. Using the SEE-Fim protocol the prevalence of EM, WN, and PTC were 45%, 33%, and 42% respectively, substantially higher than previously reported. All lesions were observed to increase with age except EM which increased until menopause then decreased dramatically. An analysis on a subset of specimens which included ovarian tissue, the prevalence of implantation of at least one lesion type (ES, WN, or PTC) was more prevalent in patients age 51 and older (93%) compared to those 31-50 years of age. We additionally developed an animal model of ES using auto-fluorescing oviductal tissue. We assessed several conditions to determine the best environment for ES lesions to grow in vivo, including supplementing with estradiol and co-administering endometrium. In this model we were able to achieve a 100% successful implantation rate of ES when oviductal tissue was administered with estradiol supplementation independent of endometrial tissue presence. When isolated OECs were used, they required endometrium, and only 10% successfully implanted. We will additionally use a model of HGSC to ascertain the importance of implantation. The prevalence of ES, as well as PTC, WN, and EM, was substantially higher than previously reported, likely due to change of protocol in pathologic evaluation. Understanding how OECs implant ectopically and give rise to HGSC will lead to truly impactful advances in early detection, potential major breakthroughs in risk assessment, and a novel treatment avenue directed at preventing implantation. Citation Format: Jan S. Sunde, Morgan Wasickanin, Tiffany A. Katz, Emily L. Wickersham, Emilie Steed, Laurel Gillette, Christine Nadeau, Novae Simper. The role of implantation in endosalpingiosis, other benign gynecologic lesions, and ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5798.