Adult stem cells are thought to be responsible for the high regenerative capacity of the human endometrium, and have been implicated in the pathology of endometriosis and endometrial carcinoma. The RNA-binding protein Musashi-1 is associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. We investigated expression and localization of Musashi-1 in endometrial, endometriotic and endometrial carcinoma tissue specimens of 46 patients. qPCR revealed significantly increased Musashi-1 mRNA expression in the endometrium compared to the myometrium. Musashi-1 protein expression presented as nuclear or cytoplasmic immunohistochemical staining of single cells in endometrial glands, and of single cells and cell groups in the endometrial stroma. Immunofluorescence microscopy revealed colocalization of Musashi-1 with its molecular target Notch-1 and telomerase. In proliferative endometrium, the proportion of Musashi-1-positive cells in the basalis layer was significantly increased 1.5-fold in the stroma, and three-fold in endometrial glands compared to the functionalis. The number of Musashi-1 expressing cell groups was significantly increased (four-fold) in proliferative compared to secretory endometrium. Musashi-1 expressing stromal cell and cell group numbers were significantly increased (five-fold) in both endometriotic and endometrial carcinoma tissue compared to secretory endometrium. A weak to moderate, diffuse cytoplasmic glandular staining was observed in 50% of the endometriosis cases and in 75% of the endometrioid carcinomas compared to complete absence in normal endometrial samples. Our results emphasize the role of Musashi-1-expressing endometrial progenitor cells in proliferating endometrium, endometriosis and endometrioid uterine carcinoma, and support the concept of a stem cell origin of endometriosis and endometrial carcinoma.

The ENZIAN-Score is presented as a new instrument to classify the deep infiltrating endometriosis. Especially the retroperitoneal part of the severe endometriosis is focussed on. In analogy to an oncological staging four different stages are pronounced. The localisation and the expansion of the endometriosis nodule was indicated to different subgroups. The still used rAFS-score is of no clinical evidence, as we pointed out in a retrospective study of our patients with severe intestinal endometriosis.

The RNA-binding protein Musashi-1 has been proposed to maintain stem cell function during development and regenerative processes as a modulator of the Notch-1 signaling pathway. Musashi-1 expression is upregulated in endometrial carcinoma, however, its pathogenetic role in this tumor entity is unknown. Here we investigate the functional impact and mode of action of Musashi-1 on endometrial carcinoma cell behaviour in vitro. Aldehyde dehydrogenase-1 activity and side population (SP) measurement by Hoechst dye exclusion revealed that the Ishikawa endometrial carcinoma cell line contains a pool of putative cancer stem cells. Musashi-1 expression is 20.8-fold upregulated in SP1 compared to SP-and equally distributed between ALDH1 and ALDH-cell pools. siRNA-mediated knockdown of Musashi-1 mRNA expression lead to an altered expression of the signaling receptor Notch-1 and its downstream targets, the transcription factor Hes-1 and the cell cycle regulators p21and cyclin B1, as determined by Western blotting and quantitative real-time PCR. Flow cytometric and ELISA analyses revealed that Musashi-1-mediated modulation of these factors exerted an antiproliferative effect on the cell cycle, and increased apoptosis in endometrial carcinoma cells. We conclude that Ishikawa cells contain a subpopulation of cells with stem cell-like properties. Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via the stemness-related factors Notch-1, Hes-1 and p21 WAF1/CIP1 , thus emerging as a novel future target for endometrial carcinoma therapy.Similar to stem cells, a subpopulation of cancer cells is characterized by a high proliferative capacity, self-renewal, expression of multidrug-resistance proteins, and a high degree of plasticity.

" Gynecological Endoscopy Study Group (Arbeitsgemeinschaft für Gynäkologische Endoskopie, AGE) " Gynecological Oncology Study Group (Arbeitsgemeinschaft für Gynäkologische Onkologie e. V., AGO) " German Society for Gynecological Endocrinology and Reproductive Medicine (Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin e. V.) " German Society for Psychosomatic Obstetrics and Gynecology (Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe, DGPFG) " German Society for General and Visceral Surgery (Deutsche Gesellschaft für Allgemeinund Viszeralchirurgie e. V., DGAV) " German Society for Urology (Deutsche Gesellschaft für Urologie e. V.

German and Austrian Societies for Obstetrics and Gynecology (Deutsche und Österreichische Gesellschaften für Gynäkologie und Geburtshilfe), Association of the Scientific Medical Societies of Germany (Arbeitsgemeinschaft der wissenschaftlichen medizinischen Fachgesellschaften, AWMF). 1.2 Funding Compilation of the present guidelines was partly financially supported by the German Society for Obstetrics and Gynecology and its Working Group Gynecologic Endoscopy (Arbeitsgemeinschaft Gynäkologische Endoskopie, AGE). 1.3 Lead professional organizations German and Austrian Societies for Obstetrics and Gynecology (DGGG and OEGGG).