{"paper_id":"aa5fbc8c-aa47-4d26-81aa-90064dd85fbf","body_text":"Jan 23, 2025\nNew evidence about malignant transformation of endometriosis - systematic\nreview\nJournal of Clinical Medicine\nDOI\nhttps://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1\nAlexandraIoannidou,NikolaosMachairiotis\nThird Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens Medical\nSchool, Attikon Hospital,1 Rimini, 124 62 Athens, Greece\nAlexandra Ioannidou\nNational Kapodistrian University of Athens\nCreate & collaborate more with a free account\nEdit and publish protocols, collaborate in communities, share insights through comments, and\ntrack progress with run records.\nCreate free account\n1 1\n1\nDOI: https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1\nExternal link: http://No external link.\nProtocolCitation: Alexandra Ioannidou, Nikolaos Machairiotis2025. New evidence about malignant transformation of\nendometriosis - systematic review.protocols.iohttps://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1\nprotocols.io | https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1 January 23, 2025 1/10\n\nManuscript citation:\nNo manuscript.\nLicense: This is an open access  protocol  distributed under the terms of the  Creative Commons Attribution License,  which\npermits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited\nProtocol status:Working\nWe use this protocol and it's working\nCreated:January 22, 2025\nLast Modified:January 23, 2025\nProtocol  Integer ID:118914\nKeywords: endometriosis, malignant transformation, EAOC, clear cell adenocarcinoma, endometrioid adenocarcinoma ,\nmalignant transformation of endometriosi, cancer among endometriosi, endometriosi, ovarian cancer, new evidence about\nmalignant transformation, malignant transformation, oncogenic pathway, uterus, cancer, disruption in chromatin remodeling,\ntargets such as the mtor pathway, chromatin remodeling, mtor pathway, clear cell adenocarcinoma, activation of oncogenic\npathway\nDisclaimer\nNot applicable.\nAbstract\nBackground: Endometriosis is a disorder in which the presence of endometrial-like tissue is found outside the\nuterus and affects 515% of women. It may undergo malignant transformation, generally presenting with ovarian\ncancers of endometrioid and clear cell adenocarcinomas, in 0.51% of women. Genetic mutations lead to\ndisruption in chromatin remodeling, particularly targeting ARID1A, and activation of oncogenic pathways, which\ninclude targets such as the mTOR pathway. Methods: The search in PubMed, Europe PMC, and Google Scholar\nwill be done comprehensively using the keywords \"endometriosis,\" \"malignant transformation,\" and \"cancer\" for\narticles ever published until December 2024. Only those studies will be included that provided information\nspecifically on the malignant transformation of endometriosis. Studies with a random diagnosis of cancer among\nendometriosis patients will be excluded. Data will be extracted by two authors using predefined criteria. \nImage Attribution\nNot applicable.\nprotocols.io | https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1 January 23, 2025 2/10\n\nGuidelines\nAccording to PRISMA 2020 checklist.\nTITLE\nThe report is identified as a systematic review. \nABSTRACT\nThis research is written according to PRISMA 2020 checklist for Abstracts.\nTitle: The report is identified as a systematic review. \nBackground: An explicit statement of the main objective the review addresses is provided.\nMethods: The inclusion and exclusion criteria for the review are specified. The information sources (e.g.\ndatabases, registers) used to identify studies and the date when each was last searched are specified. The\nmethods used to assess risk of bias in the included studies are specified. \nINTRODUCTION\nThe rationale for the review is described in the context of existing knowledge. An explicit statement of the\nobjective the review addresses is provided.\nprotocols.io | https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1 January 23, 2025 3/10\n\nMaterials\nThis systematic review will be carried out strictly according to the guidance by the PRISMA Statement. \nData sources and Search Strategy\nA systematic search of three major databases-PubMed, Europe PMC, and Google Scholar-will be performed with\nthe keywords ‘ʼendometriosis, malignant transformation, cancerʼʼ. All available articles will be considered for this\nstudy until December 2024. \nEligibility Criteria for Articles of Inclusion \nArticles have to be full-length research papers written in English, whereas abstracts presented at scientific\nmeetings, case reports and review articles will be excluded. In addition, only those studies will be included that\nprovide information specifically on the malignant transformation of endometriosis. Studies with a random\ndiagnosis of cancer among endometriosis patients will be excluded. The quality and potential risk of bias for these\nstudies will be assessed using the ROBINSI tool.\nData Extraction\nSpecific data will be extracted from each publication in duplicate, including publication date, authorship, studied\npopulation, methodologies employed, criteria for inclusion or exclusion I/E, sample type, and primary outcome\nmeasures.\nSafety warnings\nNone to declare.\nEthics statement\nNot applicable.\nprotocols.io | https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1 January 23, 2025 4/10\n\nIntroduction\n1 Endometriosis is featured by the presence of endometrial-like tissue outside the uterus\nand affects approximately 5%15% of women of reproductive age. Though usually\nbenign, about 0.5%1% of cases undergo malignant transformation, mostly into ovarian\ncancers, including endometrioid and clear cell adenocarcinomas. \nGenetic mutations, most notably in the ARID1A gene, are involved in the pathogenesis of\nEAOC; these disrupt chromatin remodeling and activate oncogenic pathways such as\nPI3K/Akt. \nBesides, the implication of the mTOR signaling pathway in the malignant transformation\nof endometriosis suggests potential therapeutic targets. \nPostmenopausal endometriosis is less frequent, but it is clinically challenging due to its\nmalignant transformation potential. Prolonged administration of estrogen-only HRT and\nhistory of definitive gynecological surgery are some of the risk factors associated with\nthe condition. \nThis systematic review seeks to synthesize recent findings in the malignant\ntransformation of endometriosis regarding genetic and molecular mechanisms, clinical\nrisk factors, and potential therapeutic interventions. The more these processes are\nunderstood, the better the diagnosis of early detection and the treatment approaches\nagainst persons at risk for EAOC.\nMaterials and Methods\n2 This systematic review will be carried out strictly according to the guidance by the\nPRISMA Statement. \nData sources and Search Strategy\nA systematic search of three major databases-PubMed, Europe PMC, and Google\nScholar-will be performed with the keywords ‘ʼendometriosis, malignant transformation,\ncancerʼʼ. All available articles will be considered for this study until December 2024. \nEligibility Criteria for Articles of Inclusion \nArticles have to be full-length research papers written in English, whereas abstracts\npresented at scientific meetings, case reports and review articles will be excluded. In\naddition, only those studies will be included that provide information specifically on the\nmalignant transformation of endometriosis. Studies with a random diagnosis of cancer\namong endometriosis patients will be excluded. The quality and potential risk of bias for\nthese studies will be assessed using the ROBINSI tool.\nprotocols.io | https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1 January 23, 2025 5/10\n\nData Extraction\nSpecific data will be extracted from each publication in duplicate, including publication\ndate, authorship, studied population, methodologies employed, criteria for inclusion or\nexclusion I/E, sample type, and primary outcome measures.\nResults\n3 Results will be presented in a standardized fashion and the publication and author data,\ndemographics, metrics, and key findings of the included studies will be tabulated to\noptimize readability.\nDiscussion\n4 A critical appraisal of the included studies will be undertaken.\nConclusion\n5 In this section, we will recapitulate the key findings of our research.\nprotocols.io | https://dx.doi.org/10.17504/protocols.io.e6nvwb2z7vmk/v1 January 23, 2025 6/10\n\nProtocol references\n     Nezhat C, Vu M, Vang N, Ganjoo K, Karam A, Folkins A, Nezhat A, Nezhat F. 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