The Pathogenesis and Prevention of Endometrial Polyps
thesisposted on 2017-07-10, 12:22 authored by Sarah Philip
Endometrial polyps are bothersome lesions, commonly seen in clinical practice causing abnormal uterine bleeding and concern about the risk of malignant transformation. The mechanisms leading to the growth of polyps is unclear. The role of altered steroid receptor expression was studied using immunohistochemistry to examine the expression of ER-α ER-β PR-A and PR-B in polyps and endometrium in women treated with and without tamoxifen. A reduction in stromal ER-β expression in polyps from both groups compared to endometrium, and a reduction in stromal PR-B expression in tamoxifen polyps compared to tamoxifen endometrium suggests that an altered sensitivity to these estrogen and progesterone is key to polyp formation. In order to examine the genetic pathways that lead to polyp formation, a cross-platform microarray was carried out that similarly examined polyps and endometrium from women treated with and without tamoxifen. A subset of 3272 polyp genes was identified. Of these, 1659 genes were upregulated in polyps relative to the endometrium, and 1613 genes down regulated in polyps relative to the endometrium. The mechanisms by which endometrial polyps are prevented in tamoxifen treated women using the LNG-IUS is thought to be via the mechanism of decidualisation. Firstly, decidualisation was confirmed in endometrial biopsy samples from tamoxifen treated women with the LNG-IUS in situ using immunohistochemistry to demonstrate an increase in IGFBP-1 expression in decidualised stromal cells. Finally, the effect of decidualisation on the expression levels 2 polyp genes, beta-catenin and Notch 2 in endometrial and polyp stromal cells, was examined by quantitative RTPCR using an in-vitro model to test the effects of medroxyprogesterone acetate, levonorgestrel and desogestrel treatment in combination with either estrogen or tamoxifen. This study demonstrated that progestin treatment did in-part reverse the polyp effect on these genes.
Supervisor(s)Taylor, Anthony; Habiba, Marwan
Date of award2017-05-14
Author affiliationDepartment of Cancer Studies & Molecular Medicine
Awarding institutionUniversity of Leicester