[Frontiers in Bioscience E3, 529-540, January 1, 2011]

Risk of carcinoma in women with ovarian endometrioma

Hiroshi Kobayashi, Hirotaka Kajihara, Yoshihiko Yamada, Yasuhito Tanase, Seiji Kanayama, Naoto Furukawa, Taketoshi Noguchi, Shoji Haruta, Shozo Yoshida, Katsuhiko Naruse, Toshiyuki Sado, Hidekazu Oi

Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan

TABLE CONTENTS

1. Abstract
2. Introduction
3. Endometriosis
3.1. Etiology and pathogenesis
3.2. Inflammatory process
4. Epithelial ovarian carcinoma (EOC)
4.1. Risk factors
4.2. Molecular genetics
5. Risk of developing EOC among women with endometriosis
5.1. Epidemiology
5.2. Morphology
5.3. Molecular genetics
5.3.1. Loss of heterozygosity (LOH)
5.3.2. K-ras and PTEN
5.3.3. P53
5.3.4. Hepatocyte nuclear factor (HNF)-1beta
5.3.5. Redox
5.3.6. Estrogen receptors (ER)
5.3.7. Wilms' tumor suppressor gene (WT1)
5.3.8. Microsatellite instability (MSI)
5.3.9. Anti-apoptosis and survival
5.3.10. Chemoresistance
6. CCC arising from clear cell adenofibroma
7. A possible novel model on molecular genetics
8. Acknowledgements
9. References

1. ABSTRACT

Endometriosis affects an estimated 10% of women in the reproductive-age group. Here, we review current knowledge on molecular genesis of endometriosis-associated epithelial ovarian carcinoma (EOC). This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Although endometriosis generally remains a benign condition, it demonstrates somatically acquired genetic alterations. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) are the most frequent types of EOC associated with endometriosis. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as iron, into the peritoneal cavity or ovarian endometrioma. CCC and EAC should be considered separately in studies of endometriosis-associated EOC. The repeated events of hemorrhage in endometriosis can contribute to carcinogenesis and progression via 3 major processes: 1) increasing oxidative stress promotes DNA methylation; 2) activating anti-apoptotic pathways supports tumor promotion; and 3) aberrant expression of stress signaling pathways contributes to tumor progression. This review summarizes recent advances in the understanding of epidemiology, carcinogenesis, pathogenesis, and pathophysiology of endometriosis-associated EOC; and a possible novel model is proposed.