{"paper_id":"cf318efa-13e9-4c42-a793-047936b1428e","body_text":"Submit Manuscript | http://medcraveonline.com\nAbbreviations: EOC, epithelial ovarian cancer; CCC, clear \ncell carcinoma; EC, endometrioid carcinoma; EOC, clear cell ca, \nand endometrioid; MMBT, mullerian or Endocervical-like mucinous \nborderline tumor; ESS, endometrial stromal sarcomas\nIntroduction\nEpithelial ovarian cancer (EOC) is the fourth gynecologic \nmalignancy. Around 50% of female deaths from cancers are due to \nthis tumour. Overall survival at 5 years in epithelial ovarian cancer is \n49.7% according to the 26th volume of the FIGO Annual Report and \nit varies between 89, 6 % in stage IA to 18.6% for stage IV .1\nEpithelial ovarian cancer presents different histological subtypes, \nmainly serous (70%), mucinous (3%), endometrioid (20–25%), clear \ncell (5–10%) mixed and undifferentiated cell (5%). The histological \nsubtypes of epithelial ovarian cancer look alike the lining of the \nfimbria of tube, endocervical, digestive epithelium, endometrium, \nrespectively and they are characterized by heterogeneous and display \ndifferent phenotypes and different molecular characterizations.2,3\nMolecular genetic studies have led to a dualistic model of origen of \nEOC. Type I ovarian tumors incorporate high-grade serous carcinomas \nwith TP53 mutations and arise from the epithelium of fimbria. On \nthe other hand, Type II ovarian carcinomas include histological types \nsuch as low-grade serous, endometrioid, clear cell, or mucinous \ncarcinomas, and it has been described KRAS or/and BRAF mutations \nand they may originate from foci of endometrial tissue via retrograde \nmenstruation.4–6 There is a meta-analysis that included 7,911 women \nwith ovarian malignancy and concluded that endometriosis is \nassociated with clear cell carcinoma (CCC) (20.2%), endometrioid \ncarcinoma (EC) (13.9%), and low-grade serous carcinoma (9.2%). 7 \nThe risk of malignant transformation of ovarian endometriosis was \n2.5 percent.7\nSampson, in 1925, put forward a connection between endometriosis \nand EOC8 and it required a pathological disgnosis of endometriosis or \nendometrial stroma in close proximity to the tumor.\nThe risk of ovarian cancer is highest in women with endometriosis \nand primary infertility. 9,10 Contrasting to other histologycal types, \nendometriosis-associated EOC is detected at a younger age and \nin lower stages. They even have lower grade lesions and a better \nprognosis.11 \nAlthough endometriosis cannot be considered as a premalignant \ndisease, it has malignant potential. Moreover, It shares with the \ncancer similar molecular events, immune disturbances, risk and \nenvironmental factors and genetic predisposition.12 \nMolecular Alteration in Endometriosis-\nassociated ovarian tumors \nThe molecular events that lead to malignant transformation of \nendometriosis is heterogeneous and may involve various reported \nprecursor lesions. Inflammation with HNF-1 Beta activation, p53 \nalteration, PTEN silencing, β-catenin, KRAS activation mutation, \nmicrosatellite instability, ARID1A inactivation mutation, PIK3CA-\nactivating mutations are involved in the occurrence of endometriosis-\nassociated EOC.13,14 \nT ypes of Endometriosis-associated ovarian \ntumors\nBetween 1966 and 2011, the literature search identified 483 \nreports describing the association between endometriosis and Ovarian \nTumors, 432 (89%) of epithe lial malignancy and only 51 (11%) about \nmesenchymal malignancy.15 EOC (Clear cell ca, and endometrioid) is \nthe most common (70%) and different types of sarcoma is the second \nmost common malignancy (12%).16 \nEndometrioid adenocarcinoma of the ovary\nAlthough an origen from endometriosis can be demonstrated in \nthe majority of cases it is not required for the diagnosis. These tumors \nusually express hormone (Estrogen and progesterone) Receptors, \nsuggesting that estrogen could be involved in carcinogenesis. 17–19 \nThe presence of endometriosis is associated with an increased risk of \nsynchronous neoplasms in the ovary and endometrium and it suggests \nthat they could share the same risk factors for their developmenty.20\nClear cell carcinoma of the ovary (CCC)\nOvarian CCC is composed of glycogen clear cells and typical \n“hobnail” cells with a low mitotic rate. They are genetically stable \nand that may contribute to their lack of sensitivity to platinum-\nbased chemotherapy. CCC is divided into two types: Cystic and \nAdenofibromatous type. Cystic clear cell carcinomas seem to \narise from endometrioma, and usually present at early stage, with \nObstet Gynecol Int J. 2020;11(4):228‒230. 228\n©2020 De la Torre-Fernández de Vega el al. This is an open access article distributed under the terms of the Creative Commons \nAttribution License, which permits unrestricted use, distribution, and build upon your work non-commercially.\nEndometriosis and ovarian cancer risk \nVolume 11 Issue 4 - 2020\nJavier de la T orre- Fernandez de Vega, Jose \nLuis Sánchez-Iglesias, Assumpt Perez- \nBenavente, Antonio Gil-Moreno\nGynaecology Oncology Unit, Hospital Vall d´Hebron, Spain\nCorrespondence: Javier de la T orre Fernández de Vega MD, \nPhD, Gynaecology Oncology Unit, Hospital Vall d´Hebron, \nBarcelona, Spain, Email \nReceived: May 31, 2020 | Published: July 22 2020\nAbstract\nEpithelial ovarian cancer presents different histological subtypes, mainly serous, mucinous, \nendometriod, clear cell, mixed and undifferentiated cell. Molecular genetic studies have \nled to a new paradigm based on a dualistic model of ovarian carcinogenesis. There is a \ncausal association between endometriosis and specific types of ovarian carcinomas, but \nthe magnitude of the risk is low and endometriosis is not considered a premalignant lesion. \nAmong the endometriosis-associated ovarian tumors adenocarcinoma is the most common \n(Endometrioid and clear cell) (70%), sarcoma is the second most common malignancy \n(12%) and rare cell types 6%. The gynecologist should pay special attention to identify \npatients with endometriosis who may be at an increased risk for ovarian cancer. \nKeywords: epithelial ovarian cancer, gynecologic malignancy, endometriosis, tumor\nObstetrics & Gynecology International Journal \nMini Review\n Open Access\n\n\nEndometriosis and ovarian cancer risk \n229\nCopyright:\n©2020 De la T orre-Fernández de Vega el al.\nCitation: De la T orre-Fernández de Vega J, Sánchez-Iglesias JL, Perez- Benavente A, et al. Endometriosis and ovarian cancer risk. Obstet Gynecol Int J. \n2020;11(4):228‒230. DOI: 10.15406/ogij.2020.11.00515\na favorable prognosis. On the other hand, the adenofibromatous \ntype or non-cystic involves the step-wise progression sequence of \nadenofibromas, atypical proliferative (borderline) tumors, and clear \ncell carcinoma. \nEndometrioid and Clear Cell adenocarcinoma are considered to \nbe “endometriosis-associated ovarian tumors”. However, they could \ncomport differently and even arise from different cells of origin.21\nAdditionally, other Müllerian-type borderline tumors could be \nassociated with endometriosis. \nSerous borderline tumor\nTypical endosalpingiosis by ectopic growth of ciliated fallo pian \ntubal-type epithelium is frequently found in SBT, but endometriosis \nwas rarely found. Endometrioid adenocarcinoma of the ovary could \nmimick SBT.22\nMullerian or Endocervical-like mucinous borderline \ntumor (MMBT)\nThe mucinous borderline tumors are of intestinal type (85-90 %) \nor Mullerian type (10-15%). MMBT is composed of endocervical like \nmucinous cells and ciliated columnar epithelium of the fimbria, and \nmay also arise from endometriosis. Even the peritoneal implants can \narise from foci of endometriosis with transformation.23 \nThe join of sarcoma (adenosarcoma and ESS) with endometriosis \nhave also been related. \nAdenosarcoma\nAdenosarcoma is an uncommon cancer that shows low malignant \npotential with a proliferation of a Müllerian- type epithelium with \nbenign, (but occasionally atypical and or malignant) features, mixed \nwith stroma. The tumor is frequently adherent to the surrounding \ntissue and many cases arise from endometriosis. A major incidence \nhas been seen in women that have received pelvic irradiation and \nhyperestrogenism, including the use of tamoxifen.24 \nEndometrial stromal sarcoma\nPrymary ovarian endometrial stromal tumors is a very rare \nmonophasic sarcomatous tumour that include stromal nodules, low-\ngrade endometrial stromal sarcomas (ESS), and undifferentiated \nendometrial sarcomas. 25 There have been reported ovarian ESS \nassociated with endometriosis.26\nConclusion\nEndometriosis is connected with an increased risk of developing \nEOC, but it is not considered a premalignant lesion. However, the \ngynecologist should pay special attention to identify patients with \novarian endometriomas, endometriosis in early age, and associated \nwith infertility which could lead to a higher chance of EOC. \nTransvaginal ultrasound is useful to identify ovarian endometrioma \nwith mural malignant changes and Magnetic resonance imaging \n(MRI) may identify malignant transformation of an endometrioma. \nTreatment options should be individualized based on the clinical \nfeatures, patient age, desire for reproduction, and oncological family \nhistory. There are no data to indicate that prophylactic extirpation of \nsites of endometriosis would be useful for reducing the risk of ovarian \ncancer. However it should be practice in women with complex \nendometriomas to exclude malignancy associated.\nNowadays, screening women with endometriosis for ovarian \ncancer is not recommended because of the low incidence and the lack \nof an effective screening test. \nThe research should be focused on identifying which women \nwith endometriosis are at risk of developing cancers and to develop \npreventative measures and curative strategies for this illness.\nAcknowledgments\nWe thank Angus Powles for all his help and dedication in this \npaper.\nFunding \nNone.\nConflicts of interest \nAll authors declare that they have no competing interests.\nReferences\n1. Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. \nFIGO 26th annual report on the results of treatment in gynecological \ncancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:S161–S192. \n2. Mutch DG, Prat J. FIGO staging for ovarian, fallopian tube and peritoneal \ncancer. Gynecol Oncol. 2014;133(3):401–404. \n3. Sørensen RD, Schnack TH, Karlsen MA, et al. Serous ovarian, fallopian \ntube and primary peritoneal cancers: a common disease or separate \nentities - a systematic review. Gynecol Oncol. 2015;136(3):571–581. \n4. Lim D, Oliva E. Precursors and pathogenesis of ovarian carcinoma. \nPathology. 2013;45(3):229–242. \n5. Kurman R, Shih L. The origin and pathogenesis of epithelial ovarian \ncancer- a proposed unifying theory. Am J Surg Pathol . 2010;34(3):433–\n443.\n6. Acién P, Velasco I, Acién M, et al. Epithelial ovarian cancers and \nendometriosis. Gynecol Obstet Invest. 2015;79(2):126–135.\n7. Pearce CL, Templeman C, Rossing MA, et al. Association between \nendometriosis and risk of histological subtypes of ovarian cancer: a \npooled analysis of case-control studies. Lancet Oncol. 2012;13:385–394.\n8. Sampson JA. Endometrial carcinoma of the ovary, arising in endometrial \ntissue in that organ. Arch Surg. 1925;10:1–2.\n9. Kumar S, Munkarah A, Arabi H, et al. Prognostic analysis of ovarian \ncancer associated with endometriosis. Am J Obstet Gynecol. 2011;204:63.\ne1–67.\n10. Wang S, Qiu L, Lang JH, et al. Prognostic analysis of endometrioid \nepithelial ovarian cancer with or without endometriosis: a 12-year cohort \nstudy of Chinese patients. Am J Obstet Gynecol. 2013;209:241.e1–249.\n11. Wang S, Qiu L, Lang JH, et al. Clinical analysis of ovarian epithelial \ncarcinoma with coexisting pelvic endometriosis. Am J Obstet  Gynecol. \n2013;208:413.e1–415.\n12. Nezhat F, Apostol R, Mahmoud M, et al. Malignant transformation of \nendometriosis and its clinical significance. Fertil Steril. 2014;102:342–\n344.\n13. Samartzis EP, Noske A, Dedes KJ, et al. ARID1A mutations and PI3K/\nAKT pathway alterations in endometriosis and endometriosis-associated \novarian carcinomas. Int J Mol Sci. 2013;14(9):18824–18849.\n14. Okamoto T, Mandai M, Matsumura N, et al. Hepatocyte nuclear factor-\n1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian \nclear cell carcinoma. Mol Carcinog. 2015;54(1):35–49. \n\nEndometriosis and ovarian cancer risk \n230\nCopyright:\n©2020 De la T orre-Fernández de Vega el al.\nCitation: De la T orre-Fernández de Vega J, Sánchez-Iglesias JL, Perez- Benavente A, et al. Endometriosis and ovarian cancer risk. Obstet Gynecol Int J. \n2020;11(4):228‒230. DOI: 10.15406/ogij.2020.11.00515\n15. Higashiura Y , Kajihara H, Shigetomi H. Identification of multiple \npathways involved in the malignant transformation of endometriosis. \nOncology Letters. 2011;4:3–9. \n16. Sayasneh A, Tsivos D, Crawford R. Endometriosis and ovarian cancer: a \nsystematic review. ISRN Obstet Gynecol. 2011:14.\n17. Gadducci A, Lanfredini N, Tana R. Novel insights on the malignant \ntransformation of endometriosis into ovarian carcinoma. Gynecol \nEndocrinol. 2014;30(9):612–627. \n18. Sieh W, Köbel M, Longacre TA, et al. Hormone-receptor expression and \novarian cancer survival: an Ovarian Tumor Tissue Analysis consortium \nstudy. Lancet Oncol. 2013;14(9):853–862.\n19. E. Oral, Aydin O, Kumbak BS, et al. Concomitant endometriosis in \nmalignant and borderline ovarian tumours. J Obstet Gynaecol. 2018;8:1–\n6.\n20. Yamanoi K, Mandai M, Suzuki A, et al. Synchronous primary corpus and \novarian cancer: High incidence of endometriosis and thrombosis. Oncol \nLett. 2012;4(3):375–380.\n21. Boyraz G, Selcuck I, Yazicioglu A, et al. Ovarian carcinoma associatedwith \nendometriosis. Eur J Obstet Gynecol Reprod Biol. 2013;170:211–213.\n22. Mansor S1, McCluggage WG. Endometrioid adenocarcinoma of the \novary mimicking serous borderline tumor: report of a series of cases. Int \nJ Gynecol Pathol. 2014;33(5):470–476.\n23. McCluggage WG. Morphological subtypes of ovarian carcinoma: a \nreview with emphasis on new developments and pathogenesis. Pathology. \n2011;43(5):420–432.\n24. Gallardo A, Prat J. Mullerian adenosarcoma: a clinicopathologic and \nimmunohistochemical study of 55 cases challenging the existence of \nadenofibroma. Am J Surg Pathol. 2009;33:278–288. \n25. Masand RP1, Euscher ED, Deavers MT, et al. Endometrioid stromal \nsarcoma: a clinicopathologic study of 63 cases. Am J Surg  Pathol. \n2013;37(11):1635–1647.\n26. Oliva E, Egger JL, Young RH. Primary endometrioid stromal sarcoma of \nthe ovary. Am J Surg Pathol. 2014;38:305–315.","source_license":"CC0","license_restricted":false}