Role of Oxidative Stress in Epigenetic Modification in Endometriosis

Ito, Fumihiko; Yamada, Yoshiaki; Shigemitsu, Aiko; Akinishi, Mika; Kaniwa, Hiroko; Miyake, Ryuta; Yamanaka, Satoshi; Kobayashi, Hiroshi

doi:10.1177/1933719117704909

Cited by 60 publications

(58 citation statements)

References 98 publications

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“…In endometriotic lesions, the expressions of ER and PR are positive, while HER2 is negative. DNA methylation due to oxidative stress decreased the expression of PR and ER; 24 the disappearance of PR especially started earlier than that of ER in case #3 (Fig. 3i,l).…”

Section: Discussionmentioning

confidence: 90%

Three cases of clear‐cell adenocarcinoma arising from endometrioma during hormonal treatments

Yokosuka

Mizutani

Ono

et al. 2018

J of Obstet and Gynaecol

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Endometrioma is known to be an occurrence site of ovarian cancer, but there is no evidence on how to reduce the risk of canceration. Here, we report three cases of ovarian cancer arising from endometrioma during hormone therapies of GnRH analogue and tamoxifen, low-dose estrogen-progestin (LEP) and dienogest. In all cases, each hormonal treatment was effective in shrinking the size of the endometrioma. During hormonal treatments, solid parts inside endometrioma were observed, which was followed by surgery. The histology of the solid parts was clear-cell adenocarcinoma in all cases. An immunohistochemistry study demonstrated that the estrogen receptor (ER) and progesterone receptor (PR) were positive in the endometriosis part but negative in the cancer part, while the human EGF receptor (HER) 2 was negative or very weak in the benign part and positive in the malignant part in all three cases. Even though hormonal treatments seem to be effective to regulate endometrioma, careful observation is needed to follow-up patients with endometrioma.

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Section: Discussionmentioning

confidence: 90%

Three cases of clear‐cell adenocarcinoma arising from endometrioma during hormonal treatments

Yokosuka

Mizutani

Ono

et al. 2018

J of Obstet and Gynaecol

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“…Epigenetic mechanisms and then genetic mutations are considered to contribute to the necessary plasticity of endometriotic cells. Recent studies have attempted to link genetic modifications with epigenetic or environmental risk factors for EAOC (23,49). These results shed light onto the mechanisms underlying the associations of environmental stimuli and redox imbalance with risk of developing EAOC.…”

Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 99%

“…Furthermore, oxidative stress (exogenous H 2 O 2 ) downregulates ARID1A mRNA and protein expression (39,52,53). Oxidative stress recruits DNA methyltransferase to chromatin (54), and also modifies the expression of CpG demethylases, such as ten-eleven translocation (TET) and jumonji (JMJ) genes (49). These genes may be involved in the development of endometriosis and its malignant transformation.…”

Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 99%

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Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

et al. 2018

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In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has diseasespecific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation ('go') and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest ('stop') under oxidative stress conditions. This model underscores a subtype-dependent 'go or stop' dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.

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“…The question whether EE of women with endometriosis bearing intrinsic anomaly as evidenced by alterations in its immune system [170,171], critical number of EE cells with stem cell characteristics [11,111] and having epigenetic modifications [172] may contribute to the development and progression of endometriosis warrants investigation. In a study of selected tumor suppressor and oncogenes in EE and autologous ET lesions obtained from women with ovarian endometriosis, Laudanski et al [118] observed higher levels of oncogene AKT1 and tumor suppressor gene product 4EBP1 mRNAs and their protein expressions in EE of women with endometriosis compared with control patients suggesting up-regulation of AKT1 and 4EBP1 in EE might be associated with the pathogenesis.…”

Section: Oncogenes and Tumor Suppressor Genesmentioning

confidence: 99%

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Ghosh

Anupa

et al. 2019

COGO

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Endometriosis is an inflammatory disease characterized by the presence of endometrium-like tissue outside the uterus primarily on pelvic organs and tissues. It affects up to 15% of women in the reproductive age group and is often associated with pelvic pain and subfertility. Different theories explain how retrograde menstruation gives rise to endometrial deposits at ectopic sites, and how several other factors are involved in the progression of the disease. Its final diagnosis is established through direct visualization at laparoscopy or surgery followed by histological confirmation. Available epidemiological reports along with histopathological observations and molecular studies shed interesting light on the pathogenetic basis of different variants of the disease like deep infiltrating endometriosis and ovarian endometriosis. Evidence also suggests that endometriosis is a neoplastic condition which serves as a precursor of ovarian and endometrial cancers. In the present review, we have attempted to take a stock of the current epidemiological and molecular knowledge regarding endometriosis associated cancers and develop a model of functional network with interactions among critical genomic factors regulating cellular processes leading to fibrotic reaction. It is being conjectured that cyclic bleeding associated with inflammatory and oxidative stress followed by repeated tissue injury and repair along with recurrent estrogenic stimulation and ovulatory events in the pelvic environment bring about the complex phenotype of atypical endometriosis and associated neoplasm with a trade-off malignant transformation in high risk population. Finally, we have presented an algorithm for pre-emptive monitoring and management of endometriosis-associated cancers.

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Role of Oxidative Stress in Epigenetic Modification in Endometriosis

Cited by 60 publications

References 98 publications

Three cases of clear‐cell adenocarcinoma arising from endometrioma during hormonal treatments

Three cases of clear‐cell adenocarcinoma arising from endometrioma during hormonal treatments

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

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