Stem cells 2013 July-28

Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells.

Hum Reprod. 2012 Nov;27(11):3187-97.

Silveira CG, Abrão MS, Dias JA Jr, Coudry RA, Soares FA, Drigo SA, Domingues MA, Rogatto SR.

Department of Genetics, Institute of Biosciences, UNESP, São Paulo State University, Botucatu, SP, Brazil.

Abstract

BACKGROUND: Endometriosis is a multifactorial gynecological disease characterized by the presence of functional endometrium-like tissue in ectopic sites. Several studies have focused on elucidating the immunological, endocrine, environmental and genetic factors involved in endometriosis. However, its pathogenesis is still unclear.

METHODS: High-resolution comparative genomic hybridization was applied to screen for genomic imbalances in laser microdissected stromal and epithelial cells from 20 endometriotic lesions and three samples of eutopic endometrium derived from eight patients. The expression of seven stemness-related markers (CD9, CD13, CD24, CD34, CD133, CD117/c-Kit and Oct-4) in endometrial tissue samples was evaluated by immunohistochemistry.

RESULTS: Samples of eutopic endometrium showed normal genomic profiles. In ectopic tissues, an average of 68 genomic imbalances was detected per sample. DNA losses were more frequently detected and involved mainly 3p, 5q, 7p, 9p, 11q, 16q, 18q and 19q. Many of the genomic imbalances detected were common to endometriotic stroma and epithelia and also among different endometriotic sites from the same patient. These findings suggested a clonal origin of the endometriotic cells and the putative involvement of stem cells. Positive immunostaining for CD9, CD34, c-Kit and Oct-4 markers was detected in isolated epithelial and/or stromal cells in eutopic and ectopic endometrium in the majority of cases.

CONCLUSIONS: The presence of shared genomic alterations in stromal and epithelial cells from different anatomical sites of the same patient and the expression of stemness-related markers suggested that endometriosis arises as a clonal proliferation with the putative involvement of stem cells.

PMID: 22940770

 

Supplementary Comments:

Research published in the open access Oxford journal Human Reproduction suggests the potential role of stem cells in endometriosis pathogenesis.

Aiming to further understand the still enigmatic pathogenesis of endometriosis, researchers from São Paulo State University, University of São Paulo, and A.C. Camargo Cancer Center investigated genomic alterations presented in the two cellular components (stroma and epithelium) of multifocal endometriotic lesions from  patients with endometriosis.

The high frequency of common genetic alterations detected in microdissected epithelial and stromal components from the lesions located in different anatomical sites lead us to hypothesize the clonal origin of the endometriotic lesions and consequently the putative involvement of stem cells in endometriosis. This hypothesis could be further supported by showing the positive immunostaining of well-known stemness-related markers (CD9, CD34, c-Kit and Oct-4) in isolated epithelial and/or stromal cells in eutopic and ectopic endometrium tissue samples primarily evaluated by High Resolution Comparative Genomic Hybridization (HR-CGH).

Currently, it has been postulated that endometriosis could be considered as a stem cell-related disease and there is evidence for the existence of stem cells in endometrial tissue. Consistent with these concepts, our study contributed to add new evidence that may support the stem cells hypothesis in endometriosis: [1] the common origin of the endometriotic lesions suggested by the high similarity of the genomic alterations found in distinct endometriotic implants by HR-CGH analysis; and [2] the expression of pluripotency markers in ectopic endometrial cells.

Furthermore, our study also described recurrent gains and losses in genomic regions harboring putative oncogenes and tumor suppressor genes associated with cell proliferation, apoptosis, inflammatory response and stromal-epithelial interactions that may represent new candidate genes associated with growth and surveillance of ectopic endometrium

Dr. Rogatto who led this research still remarked, “It is important to underscore that our study was not primarily designed to investigate the involvement of stem cells in endometriosis. The assessment of cells expressing pluripotency-related markers in endometriotic lesions was conducted based on the main finding from HR-CGH analysis. Nevertheless, our findings may greatly contribute to the debate concerning the potential role of stem cells in endometriosis pathogenesis. Certainly, future studies are necessary to better address this issue”.

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