{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:12:42Z","timestamp":1791501162792,"version":"4.3.4"},"reference-count":114,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Endometrial cysts (ECs) are thought to be the origin of endometriosis-associated ovarian cancer (EAOC). A hypothesis that the oxidative stress of iron in cysts causes \u201cmalignant transformation of ECs\u201d has been proposed, but this has not been verified. Several population-based studies showed that endometriosis was a risk factor but did not reflect the \u201cmalignant transformation of ECs\u201d. A review showed that most patients were diagnosed with EAOC early in monitoring following detection of ECs, and that these cases might have been cancer from the start. Epidemiologically, EAOC was reduced by hysterectomy rather than by cystectomy of ECs. Gene mutation analyses identified oncogenic mutations in endometriosis and normal endometrium and revealed that the same mutations were present at different endometriotic lesions. It was also shown that most of the gene mutations found in endometriosis occurred in normal endometrium. Taking together, EAOC might be caused by eutopic endometrial glandular epithelial cells with oncogenic mutations that have undergone menstrual blood reflux and engrafted in the ovary, rather than by low-risk ECs acquiring oncogenic mutations and becoming malignant. This review discusses the mechanisms of EAOC development and targeted therapy based on genetic variation in EAOC with a focus on eutopic endometrium.<\/jats:p>","DOI":"10.3390\/cancers12061676","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T10:54:59Z","timestamp":1592996099000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4278-5849","authenticated-orcid":false,"given":"Kosuke","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Kotani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekatsu","family":"Nakai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriomi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1056\/NEJMcp1000274","article-title":"Clinical practice. Endometriosis","volume":"362","author":"Giudice","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/GRF.0000000000000320","article-title":"Endometriosis-associated ovarian cancers","volume":"60","author":"Anglesio","year":"2017","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, C., Liang, Z., Liu, X., Zhang, Q., and Li, S. (2016). The association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer: Meta-analyses. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13111138"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrendo.2013.255","article-title":"Endometriosis: Pathogenesis and treatment","volume":"10","author":"Vercellini","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1097\/00003081-198023030-00024","article-title":"Malignant tumors arising in endometriosis","volume":"23","author":"Mostoufizadeh","year":"1980","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/jog.13863","article-title":"The 2017 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology. Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual patients report for 2015 and annual treatment report for 2010","volume":"45","author":"Nagase","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/humrep\/det457","article-title":"ESHRE guideline: Management of women with endometriosis","volume":"29","author":"Dunselman","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/jog.13831","article-title":"Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2017 edition","volume":"45","author":"Kawaguchi","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ejogrb.2016.04.021","article-title":"Epidemiology of endometriosis and its comorbidities","volume":"209","author":"Parazzini","year":"2017","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpobgyn.2018.06.001","article-title":"Risk for and consequences of endometriosis: A critical epidemiologic review","volume":"51","author":"Shafrir","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJMoa1700089","article-title":"Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist","volume":"377","author":"Taylor","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s00404-012-2439-7","article-title":"Oxidative stress biomarkers in patients with endometriosis: Systematic review","volume":"286","author":"Carvalho","year":"2012","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7265238","DOI":"10.1155\/2017\/7265238","article-title":"Oxidative stress and endometriosis: A systematic review of the literature","volume":"2017","author":"Scutiero","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/1078-0432.CCR-07-1614","article-title":"Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress","volume":"14","author":"Yamaguchi","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0300-483X(00)00231-6","article-title":"The Haber-Weiss reaction and mechanisms of toxicity","volume":"149","author":"Kehrer","year":"2000","journal-title":"Toxicology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1177\/1933719117704909","article-title":"Role of oxidative stress in epigenetic modification in endometriosis","volume":"24","author":"Ito","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1179\/1351000215Y.0000000038","article-title":"Potential scenarios leading to ovarian cancer arising from endometriosis","volume":"21","author":"Kobayashi","year":"2016","journal-title":"Redox Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mar\u00ed-Alexandre, J., Carcel\u00e9n, A.P., Agababyan, C., Moreno-Manuel, A., Garc\u00eda-Oms, J., Calabuig-Fari\u00f1as, S., and Gilabert-Estell\u00e9s, J. (2019). Interplay between microRNAs and oxidative stress in ovarian conditions with a focus on ovarian cancer and endometriosis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215322"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1093\/humrep\/dei462","article-title":"Endometriosis and the risk of cancer with special emphasis on ovarian cancer","volume":"21","author":"Melin","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1757-2215-3-2","article-title":"Endometriosis-associated ovarian cancer: A ten-year cohort study of women living in the Estrie Region of Quebec, Canada","volume":"3","author":"Aris","year":"2010","journal-title":"J. Ovarian Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1002\/cncr.10370","article-title":"Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women\u2019s Health Study","volume":"94","author":"Olson","year":"2002","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1525-1438.2006.00754.x","article-title":"Risk of developing ovarian cancer among women with ovarian endometrioma: A cohort study in Shizuoka, Japan","volume":"17","author":"Kobayashi","year":"2007","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10147-019-01536-5","article-title":"Endometriosis-associated ovarian cancer occurs early during follow-up of endometrial cysts","volume":"25","author":"Murakami","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1096-9098(199708)65:4<284::AID-JSO11>3.0.CO;2-2","article-title":"On the growth rates of human malignant tumors: Implications for medical decision making","volume":"65","author":"Friberg","year":"1997","journal-title":"J. Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tjog.2015.09.009","article-title":"Unexpected epithelial ovarian cancers arising from presumed endometrioma: A 10-year retrospective analysis","volume":"56","author":"Kuo","year":"2017","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, K.C., Chang, W.H., Lee, W.L., Huang, N., Huang, H.Y., Yen, M.S., Guo, C.Y., and Wang, P.H. (2014). An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-831"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1470-2045(11)70404-1","article-title":"Association between endometriosis and risk of histological subtypes of ovarian cancer: A pooled analysis of case-control studies","volume":"13","author":"Pearce","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/00000478-200212000-00001","article-title":"Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: Atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas","volume":"26","author":"Shappell","year":"2002","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1200\/JCO.2016.66.8178","article-title":"Ovarian cancer risk factors by histologic subtype: An analysis from the Ovarian Cancer Cohort Consortium","volume":"34","author":"Wentzensen","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1038\/bjc.2014.29","article-title":"Risk and prognosis of ovarian cancer in women with endometriosis: A meta-analysis","volume":"110","author":"Kim","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kurman, R.J., Ellenson, L.H., and Ronnett, B.M. (2019). Disease of the Peritoneum. Blaustein\u2019s Pathology of the Female Genital Tract, Springer. [7th ed.].","DOI":"10.1007\/978-3-319-46334-6"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1365-2559.1997.d01-592.x","article-title":"Ovarian atypical endometriosis: Its close association with malignant epithelial tumours","volume":"30","author":"Fukunaga","year":"1997","journal-title":"Histopathology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/his.13970","article-title":"Endometriosis-related pathology: A discussion of selected uncommon benign, premalignant and malignant lesions","volume":"76","author":"McCluggage","year":"2020","journal-title":"Histopathology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/humupd\/dmq030","article-title":"Tubal ligation and the risk of ovarian cancer: Review and meta-analysis","volume":"17","author":"Cibula","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/ije\/dyt042","article-title":"Tubal ligation and risk of ovarian cancer subtypes: A pooled analysis of case-control studies","volume":"42","author":"Sieh","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1159\/000357819","article-title":"Clinical characteristics of patients in Japan with ovarian cancer presumably arising from ovarian endometrioma","volume":"77","author":"Taniguchi","year":"2014","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.fertnstert.2016.07.1077","article-title":"Development of ovarian cancer after excision of endometrioma","volume":"106","author":"Haraguchi","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1158\/1055-9965.EPI-05-0394","article-title":"Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors","volume":"14","author":"Brinton","year":"2005","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/1471-0528.14793","article-title":"Impact of endometriosis on risk of further gynaecological surgery and cancer: A national cohort study","volume":"125","author":"Saraswat","year":"2018","journal-title":"BJOG"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/jnci\/djz015","article-title":"The association between hysterectomy and ovarian cancer risk: A population-based record-linkage study","volume":"111","author":"Webb","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ajog.2004.03.035","article-title":"Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis","volume":"191","author":"Modugno","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1097\/IGC.0b013e31826b5dcc","article-title":"Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma","volume":"22","author":"Ayhan","year":"2012","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1309\/AJCPZ5T2POOFMQVN","article-title":"Distinct \u03b2-catenin and PIK3CA mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas","volume":"144","author":"Matsumoto","year":"2015","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_45","first-page":"7052","article-title":"Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: Possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary","volume":"60","author":"Sato","year":"2000","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/pgp.0b013e31802b41a8","article-title":"The role of p53 mutation in the carcinomas arising from endometriosis","volume":"26","author":"Akahane","year":"2007","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1056\/NEJMoa1614814","article-title":"Cancer-associated mutations in endometriosis without cancer","volume":"376","author":"Anglesio","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.celrep.2018.07.037","article-title":"Clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium","volume":"24","author":"Suda","year":"2018","journal-title":"Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.1093\/hmg\/ddu330","article-title":"Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes","volume":"23","author":"Li","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/humrep\/dez253","article-title":"A mouse model of endometriosis mimicking the natural spread of invasive endometrium","volume":"35","author":"Wilson","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/path.5314","article-title":"Oncogenic mutations in histologically normal endometrium: The new normal?","volume":"249","author":"Lac","year":"2019","journal-title":"J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41586-020-2214-z","article-title":"The mutational landscape of normal human endometrial epithelium","volume":"580","author":"Moore","year":"2020","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/path.4516","article-title":"Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden","volume":"236","author":"Anglesio","year":"2015","journal-title":"J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ygyno.2016.07.095","article-title":"Endometriosis and risks for ovarian, endometrial and breast cancers: A nationwide cohort study","volume":"143","author":"Mogensen","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/IGC.0000000000000384","article-title":"Increased association between endometriosis and endometrial cancer: A nationwide population-based retrospective cohort study","volume":"25","author":"Yu","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3892\/ol.2012.770","article-title":"Synchronous primary corpus and ovarian cancer: High incidence of endometriosis and thrombosis","volume":"4","author":"Yamanoi","year":"2012","journal-title":"Oncol. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/IGC.0000000000000377","article-title":"Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers","volume":"25","author":"Kobayashi","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"djv427","DOI":"10.1093\/jnci\/djv427","article-title":"Massively parallel sequencing-based clonality analysis of synchronous endometrioid endometrial and ovarian carcinomas","volume":"108","author":"Schultheis","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ygyno.2016.07.114","article-title":"Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology","volume":"143","author":"Chao","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mandelbaum, R.S., Klar, M., Takiuchi, T., Bainvoll, L., Matsuzaki, S., Paulson, R.J., and Matsuo, K. (2020). Fertility-sparing treatment for early-stage epithelial ovarian cancer: Contemporary oncologic, reproductive and endocrinologic perspectives. J. Obstet. Gynaecol. Res.","DOI":"10.1111\/jog.14302"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.fertnstert.2015.06.008","article-title":"Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: Review of the results of an international multicenter study comprising 545 patients","volume":"104","author":"Bentivegna","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0002-9440(10)63653-X","article-title":"Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium","volume":"163","author":"Tanaka","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1158\/2159-8290.CD-16-0607","article-title":"Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube","volume":"6","author":"Eckert","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/path.4934","article-title":"Clear cell and endometrioid carcinomas: Are their differences attributable to distinct cells of origin?","volume":"243","author":"Cochrane","year":"2017","journal-title":"J. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1097\/PAS.0000000000000083","article-title":"Endometrioid stromal sarcoma: A clinicopathologic study of 63 cases","volume":"37","author":"Masand","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/00004347-200104000-00004","article-title":"Malignancy in endometriosis: Frequency and comparison of ovarian and extraovarian types","volume":"20","author":"Stern","year":"2001","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_68","first-page":"302","article-title":"Malignant neoplasms arising in endometriosis: Clinicopathological study of 14 cases","volume":"31","author":"Papadias","year":"2004","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_69","unstructured":"Matsumura, N., and Murakami, K. (2020). Limitations and points of conservative treatment: Carcinogenesis and early diagnosis of endometrial cysts (in Japanese). Clin. Gynecol. Obstet., in press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1093\/humrep\/det050","article-title":"Consensus on current management of endometriosis","volume":"28","author":"Johnson","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"ACOG Committee Opinion No. 774 (2019). Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet. Gynecol., 133, e279\u2013e284.","DOI":"10.1097\/AOG.0000000000003164"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ejca.2017.10.015","article-title":"Outcomes from ovarian cancer screening in the PLCO trial: Histologic heterogeneity impacts detection, overdiagnosis and survival","volume":"87","author":"Temkin","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1001\/jama.2017.21926","article-title":"Screening for ovarian cancer: US Preventive Services Task Force Recommendation statement","volume":"319","author":"Grossman","year":"2018","journal-title":"JAMA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"eaap8793","DOI":"10.1126\/scitranslmed.aap8793","article-title":"Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers","volume":"10","author":"Wang","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3332\/ecancer.2018.803","article-title":"Endometriosis and endometriosis-associated cancers: New insights into the molecular mechanisms of ovarian cancer development","volume":"12","author":"Dawson","year":"2018","journal-title":"Ecancermedicalscience"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.2353\/ajpath.2009.081000","article-title":"Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma","volume":"174","author":"Kuo","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.3802\/jgo.2016.27.e31","article-title":"Clear cell carcinoma of the ovary: Molecular insights and future therapeutic perspectives","volume":"27","author":"Mabuchi","year":"2016","journal-title":"J. Gynecol. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/gcc.22507","article-title":"Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing","volume":"57","author":"Shibuya","year":"2018","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S1470-2045(17)30469-2","article-title":"Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1\/2 mutation (SOLO2\/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"18","author":"Ledermann","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMoa1810858","article-title":"Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer","volume":"379","author":"Moore","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1056\/NEJMoa1910962","article-title":"Niraparib in patients with newly diagnosed advanced ovarian cancer","volume":"381","author":"Pothuri","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S1470-2045(20)30061-9","article-title":"Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): Post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial","volume":"21","author":"Ledermann","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1200\/JCO.2011.39.8545","article-title":"BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: A report from the Australian Ovarian Cancer Study Group","volume":"30","author":"Alsop","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.humpath.2018.10.028","article-title":"Immunohistochemistry expression of targeted therapies biomarkers in ovarian clear cell and endometrioid carcinomas (type I) and endometriosis","volume":"85","author":"Barreta","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1158\/1535-7163.MCT-10-0169","article-title":"Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary","volume":"9","author":"Mabuchi","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1056\/NEJMoa1104390","article-title":"Incorporation of bevacizumab in the primary treatment of ovarian cancer","volume":"365","author":"Burger","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1056\/NEJMoa1103799","article-title":"A phase 3 trial of bevacizumab in ovarian cancer","volume":"365","author":"Perren","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1200\/JCO.2012.42.0505","article-title":"OCEANS: A randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer","volume":"30","author":"Aghajanian","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1200\/JCO.2013.51.4489","article-title":"Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial","volume":"32","author":"Hilpert","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S1470-2045(17)30279-6","article-title":"Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology\/Gynecologic Oncology Group study GOG-0213): A multicentre, open-label, randomised, phase 3 trial","volume":"18","author":"Coleman","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1200\/JCO.2015.62.3397","article-title":"Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer","volume":"33","author":"Hamanishi","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1093\/annonc\/mdz135","article-title":"Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Results from the phase II KEYNOTE-100 study","volume":"30","author":"Matulonis","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_93","unstructured":"NIH U.S. National Library of Medicine ClinicalTrials.gov (2020, June 13). Available online: https:\/\/clinicaltrials.gov\/ct2\/home."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1056\/NEJMoa052627","article-title":"Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome","volume":"354","author":"Schmeler","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1200\/JCO.18.00283","article-title":"Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer","volume":"37","author":"Latham","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.ygyno.2017.06.027","article-title":"Prognostic impact of interleukin-6 expression in stage I ovarian clear cell carcinoma","volume":"146","author":"Kawabata","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/mc.22325","article-title":"Antitumor effects of interleukin-6 (IL-6)\/interleukin-6 receptor (IL-6R) signaling pathway inhibition in clear cell carcinoma of the ovary","volume":"55","author":"Yanaihara","year":"2016","journal-title":"Mol. Carcinog."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.1038\/ncomms7118","article-title":"Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling","volume":"6","author":"Chandler","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1196333","article-title":"Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma","volume":"330","author":"Jones","year":"2010","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1008433","article-title":"ARID1A mutations in endometriosis-associated ovarian carcinomas","volume":"363","author":"Wiegand","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/ncb3582","article-title":"ARID1A-mutated ovarian cancers depend on HDAC6 activity","volume":"19","author":"Bitler","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.1158\/0008-5472.CAN-19-1302","article-title":"HDAC6 Inhibition Synergizes with Anti-PD-L1 Therapy in ARID1A-Inactivated Ovarian Cancer","volume":"79","author":"Fukumoto","year":"2019","journal-title":"Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s00109-016-1395-2","article-title":"Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer","volume":"94","author":"Er","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrfmmm.2018.03.001","article-title":"The presence of KRAS, PPP2R1A and ARID1A mutations in 101 Chinese samples with ovarian endometriosis","volume":"809","author":"Zou","year":"2018","journal-title":"Mutat. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/humrep\/dey332","article-title":"Iatrogenic endometriosis harbors somatic cancer-driver mutations","volume":"34","author":"Lac","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1136\/jclinpath-2016-203776","article-title":"Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma: An analysis of 63 patients","volume":"69","author":"Zannoni","year":"2016","journal-title":"J. Clin. Pathol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/bjc.2017.228","article-title":"Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma","volume":"117","author":"Itamochi","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1016\/j.ajpath.2017.06.012","article-title":"Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks","volume":"187","author":"Murakami","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ygyno.2016.11.045","article-title":"Identification of novel mutations in Japanese ovarian clear cell carcinoma patients using optimized targeted NGS for clinical diagnosis","volume":"144","author":"Maru","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"14754","DOI":"10.18632\/oncotarget.24546","article-title":"Affinity-purified DNA-based mutation profiles of endometriosis-related ovarian neoplasms in Japanese patients","volume":"9","author":"Ishikawa","year":"2018","journal-title":"Oncotarget"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ygyno.2017.12.005","article-title":"Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing","volume":"148","author":"Kim","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.humpath.2018.11.013","article-title":"PIK3CA hotspot mutations and cyclooxygenase-2 expression in ovarian clear cell carcinomas: A close association with stromal features","volume":"86","author":"Kato","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2019.03.003","article-title":"Targeted sequencing of a specific gene panel detects a high frequency of ARID1A and PIK3CA mutations in ovarian clear cell carcinoma","volume":"494","author":"Su","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1507\/endocrj.EJ19-0283","article-title":"Identification of novel mutations of ovarian cancer-related genes from RNA-sequencing data for Japanese epithelial ovarian cancer patients","volume":"67","author":"Nagasawa","year":"2020","journal-title":"Endocr. J."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1676\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:42:28Z","timestamp":1760175748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,24]]},"references-count":114,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cancers12061676"],"URL":"https:\/\/doi.org\/10.3390\/cancers12061676","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,24]]}}}