In this prospective trial, patients with enhanced clinical risk and omitted chemotherapy on the basis of RS ≤ 11 had excellent 3-year survival. The substantial discordance observed between traditional prognostic markers and RS emphasizes the need for standardized assessment and supports the potential integration of standardized, well-validated genomic assays such as RS with clinicopathologic prognostic factors for chemotherapy indication in early hormone receptor-positive BC.
Uterine epithelial cells from normal human endometrium were cultured as a primary cell culture in a dual-chambered system. The epithelial cells were isolated from endometrial tissue of the proliferative phase obtained by hysterectomy. The epithelial cells were seeded on Millicell CM filters coated with the extracellular matrix Matrigel. Depending on the culture conditions, the epithelial cells formed a polarized cell monolayer on Matrigel or gland-like structures in Matrigel. The epithelial cell polarity was maintained during culture, which could be proved by electron microscopy. The progesterone and estrogen receptors as typical marker molecules for physiologically intact endometrial epithelial cells could be detected immunohistochemically as well as by RT-PCR in vitro and were down-regulated by medroxyprogesterone acetate (MPA) used as progesterone analogue. As this cell culture system exhibits morphological and immunohistochemical characteristics, typical for the in vivo situation, and since it can be modulated by hormone treatment under the in vitro conditions described, it represents a valuable tool for investigating processes that are essential for endometrial differentiation and reproductive functions.
Expression of connexins, the proteins which comprise gap junction channels, is regulated by ovarian hormones in the female reproductive tract of rodents. In order to determine if these hormones also affect connexin expression in the human uterus, the distribution patterns of different connexins (cx26, cx32, cx43) were investigated by immunohistochemistry in human endometrial tissue collected throughout the menstrual cycle. During the early proliferative phase of the cycle extremely low staining for connexin 43 was observed and connexin 26 antigens could not be detected. An increase in the amount of connexin 43 in stromal cells and of connexin 26 in glandular and luminal epithelial cells was seen from days 11-15 of the cycle. Following ovulation, the expression of both connexins was suppressed and was completely abolished in the late secretory phase. Weak staining for connexin 32 was found mainly in the late proliferative and the early secretory phase and was restricted to the basal membrane region of the glandular cells. These results suggest that the different connexins could represent cell biological markers for the proliferation and differentiation of the human endometrium throughout the menstrual cycle.
The serum levels of FSH, LH and estradiol-17 beta (E2) were determined in 110 women aged between 38-48 years who had been hysterectomized 2-10 years previously and were compared with a control group (n = 112). In hysterectomized women both FSH and LH levels were higher than in controls during the whole 12 year period. These differences were significant up to 43 years of age. The hypergonadotropism in hysterectomized women correlates with the higher incidence of climacteric symptoms reported in the literature.
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