Comprehensive Analysis of Leukocytes, Vascularization and Matrix Metalloproteinases in Human Menstrual Xenograft Model

In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation

Is lymphadenectomy a prognostic marker in endometrioid adenocarcinoma of the human endometrium?

<p>Abstract</p> <p>Background</p> <p>During surgery for endometrial cancer, a pelvic lymphadenectomy with or without para-aortic lymphadenectomy is performed at least in patients with risk factors (stage I, grading 2 and/or histological subtypes with higher risk of lymphatic spread), and is hence recommended by the International Federation of Obstetrics and Gynecology (FIGO). Although lymph node metastases are important prognostic parameters, it has been contentious whether a pelvic lymph node dissection itself has a prognostic impact in the treatment of endometrial cancer, especially in endometrioid adenocarcinoma. Therefore, this study evaluated whether lymphadenectomy has a prognostic impact in patients with endometrioid adenocarcinoma.</p> <p>Methods</p> <p>The benefits of lymphadenectomy were examined in 214 patients with a histological diagnosis of endometrial adenocarcinoma. Tumour characteristics were analysed with respect to the surgical and pathological stage.</p> <p>Results</p> <p>Of the 214 patients with endometrial adenocarcinoma, 171 (79.9%) were classified as FIGO stage I, 15 (7.0%) FIGO stage II, 21 (9.8%) FIGO stage III and 7 (3.3%) FIGO stage IV. One hundred and thirty four (62.6%) of the patients had a histological grade 1 tumour, while 56 (26.2%) and 24 (11.2%) had a histological grade 2 or grade 3 tumour, respectively. Lymphadenectomy was performed in 151 (70.6%) patients. Only 11 (5.1%) patients showed metastatic disease in the lymph nodes. The performance of a lymphadenectomy resulted in significantly increased cause-specific and overall survival, while progression-free survival was not affected by this operative procedure.</p> <p>Conclusions</p> <p>The performance of an operative lymphadenectomy resulted in better survival of patients with endometrioid adenocarcinoma. This increase was significant for cause-specific and overall survival, while there was a tendency only towards increased progression-free survival. Therefore, even in endometrioid adenocarcinoma, a pelvic and/or para-aortic lymphadenectomy should be performed.</p