The Dichotomy in the Histogenesis of Endometriosis-associated Ovarian Cancer

Abstract

The histogenesis of endometriosis and endometriosis-associated ovarian cancer is one of the most mysterious aspects of pathology. To better understand the histogenesis of endometriosis and endometriosis-associated ovarian cancer, we analyzed the possibility of a link of endometrium, ovarian surface epithelium, and a cortical inclusion cyst to ovarian endometriosis and endometriosis-associated ovarian cancer by immunohistochemistry using the epithelial membrane antigen (an epithelial marker), calretinin (a mesothelial marker), and hepatocyte nuclear factor (HNF)-1β (a clear cell carcinoma-specific transcription factor). During ovarian surface epithelium invagination, cortical inclusion cyst epithelial cells may, in some cases, undergo mesothelial-epithelial transition and subsequently differentiate into endometriosis. This case of endometriosis that has undergone Müllerian metaplasia arises from the HNF-1β-negative cells. The remaining endometriosis may develop from the late secretory and menstrual endometria, with HNF-1β-positive staining, by retrograde menstruation. Endometrioid adenocarcinoma and clear cell carcinoma arise from the HNF-1β-negative and HNF-1β-positive epithelial cells of endometriosis, respectively. It has been proposed that clear cell and endometrioid-type adenocarcinomas arise from distinct types of endometriosis with different cells of origin.

Ovarian Clear Cell Carcinoma Detected During Long-Term Management of Endometriotic Cysts in Young Patients: Possible Heterogeneity of this Tumor

“…Epidemiological studies have shown that oral contraceptives prevent ovarian cancer and the risk decreases further as the age of starting contraceptive therapy declines and the duration of treatment increases [8]. It was recently proposed that ovarian cancer may arise from endometriotic cysts via 2 modes of carcinogenesis, which are a hormone-dependent pathway for the endometrioid subtype and a hormone-independent pathway for the clear cell subtype [9,10]. Based on this hypothesis, Vercellini et al [11] suggested that chemoprophylaxis by long-term oral contraceptive therapy would mainly suppress endometrioid carcinoma, since this tumor expresses both ER DOI: 10.1159/000494256…”

Malignome auf dem Boden einer Endometriose

“…Weitere Mutationen, die bei endometrioseassoziierten Malignomen identifiziert wurden, betreffen CTNNB1 ("catenin beta-1"; [28] und HNF1β ("hepatocyte nuclear factor 1 beta"). Eine Überexpression von HNF1β kommt in klarzelligen Ovarialkarzinomen sowie in atypischen und gewöhnlichen Endometriosen vor, jedoch wohl nicht in endometrioiden Ovarialkarzinomen [1,18].…”

A new classification of ovarian tumors

“…Изменилось представление о пато-генезе этих опухолей: принята теория развития светлокле-точных карцином из очагов эндометриоза, предложенная H. Kajihara и соавт. [10] и подтвержденная обнаруженны-ми генетическими изменениями.…”