Background: Endometriosis in endometriosis-associated ovarian cancer (EAOC) refers to lesions that can derive from endometriotic ovarian cysts (ECs) that form in the ovarian endometrium with the potential to transform into full-blown ovarian cancer. Hypomethylation of long interspersed element-1 (LINE-1 or L1) is a common epigenomic event in several cancers and is strongly associated with ovarian cancer progression.
Objectives: To evaluated alterations in LINE-1 methylation between EC, ovarian endometrioid adenocarcinoma (OEA), EAOC, and ovarian clear cell carcinoma (OCC).
Methods/ Materials: First, LINE-1 methylation status in 19 normal endometrium, 29 EC, 35 OCC, and 22 OEA tissues from unrelated samples were compared. Then, specific areas of eutopic endometrium, contiguous endometriosis, and cancer arising from 16 EAOCs were collected by microdissection and analyzed for LINE-1 methylation status.
Results: The total LINE-1 methylation levels were significantly different among the endometrium, endometriosis, and ovarian cancer (P < 0.001). A stepwise decrease in LINE-1 methylation was observed in the following order: normal endometrium, EC, OEA, and OCC. Interestingly, endometriosis in EAOC of both OEA (P = 0.016) and OCC (P = 0.003) possessed a higher percentage of LINE-1 unmethylated loci than EC.
Conclusion: Our data implicate that LINE-1 hypomethylation is an early molecular event involved in OEA and OCC malignant transformation. Precise measurements of LINE-1 methylation may help to distinguish EC and endometriosis in EAOC.
*Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University; †Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University; ‡Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University; and §Gynecologic Cytopathology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Address correspondence and reprint requests to Apiwat Mutirangura, MD, PhD, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. E-mail: firstname.lastname@example.org; email@example.com.
This study was supported by a Research Chair Grant 2011 from the National Science and Technology Development Agency in Thailand at the Center of Excellence in Molecular Genetics of Cancer and Human Diseases at Chulalongkorn University and the Ratchadapiseksomphot Fund from the Faculty of Medicine at Chulalongkorn University.
NK was supported by Thailand Research Funds (RSA 5580013). The remaining authors declare no conflicts of interest.
Received May 29, 2013
Accepted September 15, 2013