Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy

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 “malignant transformation of ECs” has been proposed, but this has not been verified. Several population-based studies showed that end...

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Published inCancers Vol. 12; no. 6; p. 1676
Main Authors Murakami, Kosuke, Kotani, Yasushi, Nakai, Hidekatsu, Matsumura, Noriomi
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 24.06.2020
MDPI
Subjects
Age
Cancer therapies
Cysts
Deoxyribonucleic acid
DNA
DNA damage
DNA methylation
Endometriosis
Endometrium
Epidemiology
Epithelial cells
Genetic diversity
Genetic transformation
Health risk assessment
Hypotheses
Hysterectomy
Infertility
Menopause
Menstruation
Mutation
Opinion
Ovarian cancer
Oxidative stress
Pain
Point mutation
Population studies
Risk factors
Surgery
Ultrasonic imaging
Womens health
Japan
Taiwan
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Abstract 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 “malignant transformation of ECs” 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 “malignant transformation of ECs”. 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.
AbstractList 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 “malignant transformation of ECs” 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 “malignant transformation of ECs”. 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.
Author Kotani, Yasushi
Murakami, Kosuke
Matsumura, Noriomi
Nakai, Hidekatsu
AuthorAffiliation Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan; kmurakami@med.kindai.ac.jp (K.M.); y-kotani@med.kindai.ac.jp (Y.K.); nakai@med.kindai.ac.jp (H.N.)
AuthorAffiliation_xml – name: Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan; kmurakami@med.kindai.ac.jp (K.M.); y-kotani@med.kindai.ac.jp (Y.K.); nakai@med.kindai.ac.jp (H.N.)
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  surname: Nakai
  fullname: Nakai, Hidekatsu
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  givenname: Noriomi
  surname: Matsumura
  fullname: Matsumura, Noriomi
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Snippet 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...
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StartPage 1676
SubjectTerms Age
Cancer therapies
Cysts
Deoxyribonucleic acid
DNA
DNA damage
DNA methylation
Endometriosis
Endometrium
Epidemiology
Epithelial cells
Genetic diversity
Genetic transformation
Health risk assessment
Hypotheses
Hysterectomy
Infertility
Menopause
Menstruation
Mutation
Opinion
Ovarian cancer
Oxidative stress
Pain
Point mutation
Population studies
Risk factors
Surgery
Ultrasonic imaging
Womens health
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Title Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy
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Volume 12
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