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Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay
Open accessAbstract
Objective To determine the clonal origins of endometriotic lesions using laser capture microdissection and PCR-based HUMARA assay.Design Molecular genetic study of human tissue.Setting Molecular genetics laboratory in an academic setting.Patient(s) Twenty patients with endometriosis. Forty specimens of endometriotic lesions from these patients and one specimen of normal endometrium were analyzed.Intervention(s) Laser capture microdissection was used to harvest epithelial cells from single and multifocal endometrial lesions from paraffin-embedded and frozen tissues, and their clonality was determined with the HUMARA assay.Main outcome measure(s) Polymerase chain reaction-based HUMARA assay of clonality.Result(s) Thirty-eight specimens were polymorphic and thus informative. Most specimens were monoclonal, as determined by the HUMARA assay. In four specimens of multifocal lesions, polyclonality was detected, but upon more refined microdissections and further analyses, we found that each focus was monoclonal individually.Conclusion(s) Previously reported polyclonality is very likely to be attributed to the pooling of multifocal lesions or contamination of normal tissues. These results suggest that endometriotic lesions were monoclonal in origin, and in the case of multifocal lesions, each focus originates monoclonally; hence, different foci have independent origins. The monoclonality of endometriotic lesions suggests that they may carry neoplastic potentials, and the apparent independent origins of multifocal lesions suggest that reconstruction of individual lesion histories may help us to understand the initiation and progression of endometriosis.
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“Endometriosis lesions are clonal, as demonstrated for typical (149), deep (150), and cystic ovarian (151-153) endometriosis.”
From Pathogenesis of endometriosis: The genetic/epigenetic theory (2019) · cites this paper as [149]
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“A strong argument is that deep (174, 175) and cystic (176-178) ovarian endometriosis are consistently found to be clonal in origin.”
From Pathogenesis of deep endometriosis (2017) · cites this paper as [175]
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Koninckx, P. R., Ussia, A., Adamyan, L. V., Wattiez, A., & Viganò, P. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14207196 · Cited by 3
The Genetic-Epigenetic Pathophysiology of Endometriosis: A Surgeon’s View
Koninckx, P. R., Ussia, A., Adamyan, L. V., Keckstein, J., Wattiez, A., Gomel, V., & Martin, D. C. (2020) · Springer eBooks · doi:10.1007/978-3-030-52984-0_6 · Cited by 3
NOTCH1- and CD117-Positive Stem Cells in Human Endometriosis and Adenomyosis Lesions
Metodiev, D., Parvanov, D. A., Ruseva, M., Ganeva, R., Handzhiyska, M., Vidolova, N., Chavoushian, A., Hadjidekova, S. P., & Stamenov, G. (2024) · Diagnostics · doi:10.3390/diagnostics14151642 · Cited by 3
Endometriosis and ovarian cancer
Brown, D., Pejovic, T. B., & Nezhat, F. R. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139003254.015 · Cited by 3
Etiologies of endometriosis and model systems: is there a risk of a tunnel vision?
Manavalan, M. A., Babtain, M., Weessies, M., Nap, A. W., Verdurmen, W. P. R., Taurin, S., Sater, M. S., & Brock, R. E. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1675051 · Cited by 3
Endometrial Determinism of Endometriosis: An Unnecessary Adjunct to Retrograde Menstruation
Habiba, M. A., Guo, S., & Benagiano, G. (2024) · Current Obstetrics and Gynecology Reports · doi:10.1007/s13669-024-00378-x · Cited by 3
Genetics of Female Infertility in Humans
Bhagavath, B., & Layman, L. C. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00040-9 · Cited by 2
Cells with “Stemness”: Seeds for endometriosis?
Shetty, D., Chaudhari, U. K., & Sachdeva, G. (2016) · Journal of Reproductive Health and Medicine · doi:10.1016/j.jrhm.2016.10.005 · Cited by 2
Recent Advances in Molecular Genetics of Endometriosis
Silveira, C. G. T., Rogatto, S. R., Podgaec, S., & Abrão, M. S. (2009) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.1177/228402650900100103 · Cited by 2
Role of Stem Cells in the Pathogenesis of Endometriosis
Maruyama, T. (2014) · Springer eBooks · doi:10.1007/978-4-431-54421-0_4 · Cited by 1
Recent advances in molecular genetics of endometriosis
Silveira, C. G. T., Rogatto, S. R., Podgaec, S., & Abrão, M. S. (2009) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/je.2009.1980 · Cited by 1
Metadata
- Authors
- Wu, Y., Basir, Z., Kajdacsy-Balla, A., Strawn, E., Macias, V., Montgomery, K., & Guo, S.-W.
- Affiliations
- Medical College of Wisconsin (US)
- Corresponding author
- Guo, Sun-Wei
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 79
- Pages
- 710-717
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2048646241
- Cited by
- 114
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 10 · 2014: 8 · 2013: 6 · 2012: 9
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical College of Wisconsin
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Health Sciences › Medicine › Obstetrics and Gynecology › Ectopic Pregnancy Diagnosis and Management
- Keywords
- endometriosis, endometriotic lesions, clonal origin, monoclonality, polyclonality, multifocal lesions, HUMARA assay, human androgen receptor, laser capture microdissection, endometrial epithelium, neoplastic potential
- MeSH terms
- Adult, Clone Cells, DNA, Neoplasm, Endometriosis, Epithelial Cells, Female, Histocytochemistry, Humans, Lasers, Micromanipulation, Middle Aged, Receptors, Androgen, DNA-Cytosine Methylases, Polymerase Chain Reaction, Sequence Analysis, DNA
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