Independent development of endometrial epithelium and stroma within the same endometriosis

Noë, Michaël; Ayhan, Ayşe; Wang, Tian Li; Shih, Ie Ming

doi:10.1002/path.5082

Cited by 57 publications

(52 citation statements)

References 22 publications

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“…According to this hypothesis, histopathologically there are three types of nodules seen in the course of histogenesis of endometriosis: type 1 nodules are formed from the endometrial stromal cells, followed by transformation of the mesothelium into endometrial glands as seen in type 2 nodules and type 3 nodules due to the inductive actions of the endometrial stroma, while other factors of genetic, hormonal and immunological origin affect the proliferative and replicative capacities. The above paradigm is somewhat corroborated by the report of Noe et al [43], according to which ET lesions may co-develop from independent progenitors for epithelial and stromal cells, since epithelium found clonally and developmentally distinct from stroma and originating from a single circulating endometrial epithelial progenitor cell in the ET niche; it was presumed that these endometrial epithelial progenitor cells do carry "driver" and "passenger" mutations and undergo clonal expansion to form glandular tissue at the ET site [43]. The authors further suggested that blood-borne mesenchymal stem cells might migrate and home at the prospective ET site due to chemotactic activity associated with inflammation and tissue repair and then proliferate giving rise to the stromal component.…”

Section: Introductionsupporting

confidence: 73%

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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Section: Introductionsupporting

confidence: 73%

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

Ghosh

Anupa

et al. 2019

COGO

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“…Studies are awaited to determine the presence or the involvement of cells expressing N-cadherin and other endometrial stromal ASC markers in ectopic endometriotic lesions formation. Interestingly, a recent study which analysed synonymous and missense somatic passenger mutations has suggested that ectopic endometriotic lesions contain clonal populations of epithelial cells originating from, presumably, an ectopically situated epithelial ASC, whereas stromal cells may be continuously regenerated or recruited over the course of disease [ 144 , 145 ]. This data presents a novel concept, in that the primary cell type initiating and regulating the initiation as well as persevering the ectopic lesions could be the epithelial ASC and they may subsequently recruit stromal ASCs to create the endometrial niche.…”

Section: Involvement Of Endometrial Stem Cells In Endometrial Prolmentioning

confidence: 99%

Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions

Tempest

Maclean

Hapangama

2018

IJMS

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The human endometrium is a highly regenerative organ undergoing over 400 cycles of shedding and regeneration over a woman’s lifetime. Menstrual shedding and the subsequent repair of the functional layer of the endometrium is a process unique to humans and higher-order primates. This massive regenerative capacity is thought to have a stem cell basis, with human endometrial stromal stem cells having already been extensively studied. Studies on endometrial epithelial stem cells are sparse, and the current belief is that the endometrial epithelial stem cells reside in the terminal ends of the basalis glands at the endometrial/myometrial interface. Since almost all endometrial pathologies are thought to originate from aberrations in stem cells that regularly regenerate the functionalis layer, expansion of our current understanding of stem cells is necessary in order for curative treatment strategies to be developed. This review critically appraises the postulated markers in order to identify endometrial stem cells. It also examines the current evidence supporting the existence of epithelial stem cells in the human endometrium that are likely to be involved both in glandular regeneration and in the pathogenesis of endometrial proliferative diseases such as endometriosis and endometrial cancer.

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mentioning

confidence: 72%

“…The current study by Noë et al is an extension of work published by this team in 2017 . By focusing the analysis on passenger mutations within endometriotic lesions, this study presents intriguing findings that provide insights into the origins of this complex disease . From the perspective of the stem cell theory, Noë et al sought to elucidate whether epithelial and stromal cells from the same endometriotic lesions are clonally derived from the same progenitor/stem cells .…”

mentioning

confidence: 91%

“…By focusing the analysis on passenger mutations within endometriotic lesions, this study presents intriguing findings that provide insights into the origins of this complex disease . From the perspective of the stem cell theory, Noë et al sought to elucidate whether epithelial and stromal cells from the same endometriotic lesions are clonally derived from the same progenitor/stem cells . Previously, this group had performed whole‐exome sequencing of mixed endometriotic lesions (consisting of epithelium and stroma), and identified various passenger mutations (synonymous and missense mutations) within lesions .…”

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confidence: 99%

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Distinct developmental trajectories of endometriotic epithelium and stroma: implications for the origins of endometriosis

Lac

Huntsman²

2018

The Journal of Pathology

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Endometriosis is a common gynecological disease characterized by the ectopic growth of endometrium-like tissue. Despite the widespread prevalence of endometriosis, its pathogenesis remains poorly understood. A recent study by Noë et al provides evidence that the epithelium and stroma within the same endometriotic lesions follow distinct and independent developmental trajectories. They used droplet digital polymerase chain reaction analysis of laser-captured epithelium-enriched and stroma-enriched endometriosis tissue, and found that all 19 somatic passenger mutations analyzed were enriched exclusively in the epithelial compartment. These findings are consistent with the clonal expansion of epithelial cells, whereas stromal cells may be continuously regenerated or recruited over the course of disease. Further findings of differing allelic frequencies among passenger mutations within the epithelium of the same endometriotic lesions are suggestive of subclonality or the existence of multiple clones in some cases. Overall, the authors' observations of clonally dominant somatic passenger mutations in the epithelium and not the stroma of endometriosis add to the recent description of cancer-associated mutations in such lesions, and provide clues to the pathogenesis of endometriosis. Further studies to determine where and when these mutations occur and whether they can be used to develop the first biologically informed classification system for endometriosis are warranted. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Independent development of endometrial epithelium and stroma within the same endometriosis

Cited by 57 publications

References 22 publications

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

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

Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions

Distinct developmental trajectories of endometriotic epithelium and stroma: implications for the origins of endometriosis

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