Epithelial Mutations in Endometriosis: Link to Ovarian Cancer.

Epithelial Mutations in Endometriosis: Link to Ovarian Cancer. Endocrinology. 2019 Jan 17;: Authors: Bulun SE, Wan Y, Matei D Abstract While epidemiologic and histopathologic associations between endometriosis and epithelial ovarian cancer have been reported, the underlying molecular and cellular mechanisms are not well understood. Recent publications suggest a possible genetic link. Driver mutations in PIK3CA, KRAS, ARID1A and other genes have been found in the epithelium of intrauterine endometrial tissue, ovarian and extraovarian pelvic endometriosis tissue, ovarian cancers associated with endometriosis (clear cell and endometrioid type) and other epithelial ovarian cancers. This makes sense because pelvic endometriosis occurs primarily as a result of retrograde menstruation and implantation of endometrial tissue fragments in ovarian inclusion cysts or extraovarian peritoneal or subperitoneal sites. In contrast to epithelial cells, endometriotic stromal cells are mutation-free but contain widespread epigenetic defects that alter gene expression and induce a progesterone-resistant and intensely inflammatory environment, driven by estrogen via estrogen receptor-β. The resulting increase in estrogenic action in the stroma drives inflammation and sends paracrine signals to neighboring epithelial cells to enhance proliferation. There may be an additional factor unique to the ovarian microenvironment. Massively high concentrations of e...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research