The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1 estrogen regulated genes implicated in proliferation is increased in peritoneal endometriosis

Capsule:
The expression of E receptors as well as GREB1, Cyclin D1, and c-myc is increased in peritoneal endometriotic lesions compared with control eutopic endometrium.

Authors:
Chiara Pellegrini, M.Sc., Ilaria Gori, Ph.D., Chahin Achtari, M.D., Daniela Hornung, M.D., Ph.D., Eric Chardonnens, M.D., Dorothea Wunder, M.D., Maryse Fiche, M.D., and Geraldine O. Canny, Ph.D.

Volume 98, Issue 5, Pages 1200-1208, November 2012

Abstract:

Objective:
To analyze the expression of estrogen receptor α and β as well as their target genes implicated in proliferation, c-myc, Cyclin D1 and GREB1 in the endometrium of women with or without endometriosis.

Design:
Expression analysis in human tissue.

Setting:
University Hospital and clinic.

Patients:
91 premenopausal women (59 endometriosis patients and 32 controls) undergoing laparoscopic surgery.

Intervention:
Biopsies were obtained at time of surgery, performed during the proliferative phase of the cycle.

Main Outcome Measure(s):
Estrogen receptors α and β as well as c-myc, Cyclin D1 and GREB1 mRNA expression levels were quantified by qRT-PCR. Tissue localization of these estrogen-regulated genes was analyzed by immunohistochemistry.

Results:
Estrogen receptors α and β as well as c-myc, Cyclin D1 and GREB1 mRNA expression levels were increased in ectopic in comparison to both normal and eutopic endometrium. Estrogen receptor mRNA levels were also upregulated in eutopic peritoneal tissue of endometriosis patients. Cyclin D1 and GREB1 expression was augmented in eutopic endometrium. c-myc, Cyclin D1 and GREB1 proteins exhibited a nuclear localization in ectopic endometrial tissue.

Conclusions:
This constitutes the first report of increased expression of GREB1, as well as cyclin D1 and c-myc, in peritoneal endometriotic lesions, implicating these proteins in estrogen-dependent growth in this context.

  • Juan Garcia-Velasco, MD

    Congratulations on your paper! Very interesting data trying to understand the behaviour of ectopic implants. Do you think this might explain why some women have a very aggressive disease, and have severe recurrences a few months after surgery and do not respond well to medications, while others remain stable for years?

    • Thank you and I only saw this message now, hence the late reply. It is difficult to answer as estrogen signaling is a “story” of estrogens, E2 being the most potent, different receptors which are likely regulated in different ways and metabolites (which however, have lower ER binding affinity). By “aggressive”, do you mean more lesions or more pain? This is difficult to assess as they are not correlated, this is the problem with rAFS staging. Also, many women are assyptomatic. Responses to medications is likely due to several factors. In order to answer this question we need well-defined patient cohorts and a definition of “remission” and proper follow-up, to also define treatment efficacy. Many more studies are needed.
      I would be interested to know what you mean by “stable”.

      • Juan Garcia-Velasco, MD

        Thanks for your answer. Agree with you that it is not an easy area; “agressive” means both, lesions and pain that take these women to surgery again; “stable” are those that regardless time, no more lesions are observed and no worsening of their QoL.

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