子宮内膜症の病理形態と発育増殖

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  • Morphological Appearance and Growth of Pelvic Endometrosis

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We investigated the relationship between morphological appearance proposed by r-ASRM classificaion and its activity and examined the influence of hepatocyte growth factor (HGF) and macrophage on the growth and maintenance of pelvic endometriosis. 1. Morphological appearance and activity of endometriotic lesions. Color appearance for endometriosis is roughly divided into 3 groups, red, black and white lesion. We investigated immunohistochemical staining of PCNA as a cell-proliferative marker and Endoglin as an angio-genic marker in these 3 groups. PCNA index and expression rate of endoglin-positive cells were the most highest in red lesion, intermediate in black lesion and the lowest in white lesion. We measured HGF, IL-6 and VEGF in peritoneal fluid by ELISA, subdividing red lesions into transparent and opaque lesions. HGF, IL-6 and VEGF concentrations in peritoneal fluid was the most highest in women with opaque red lesion, intermediate in black lesion, and the lowest in white lesion. 2. Morphological change of mesothelial cells in peritoneum adjacent to endometriotic lesion. Mesothelial cells adjacent to red and black lesion had changed to cuboidal or columnar epithelium. Expression of estrogen and progesterone receptor-mRNA was recognized in morphologically altered peritoneum by nonradioactive in situ hybridization using thymine-thymine dimerized oligonucleotide probes. The tissue with atypical glandular epithelium or stromal tissue alone without glandulan structures, which is called atypical endometriosis, was recognized in peritoneal tissue adjacent to typical endometriotic lesion. Estrogen and progesterone receptors were expressed in these atypical endometriosis. We need to consider these findings when conducting laparoscopic operation as a state of pre-endometriosis which might exist in tissue adjacent to endometrioticlesion. 3. Influence of HGF on the growth of endometriotic lesion. HGF induces peritoneal mesothelial cell to c olumnar epithelium and lumen formation in cultured endometrial epithelium. Localization of HGF and c-Met producing cell was examined in eutopic and ectopic endometrium by immunohistochemical staining. Intensity of immunostaining was expressed by Q-H scores. Q-H scores of HGF and c-Met in eutopic endometrium with endometriosis were higher than control in both epithelium and stroma. Q-H scores of HGF and c-Met in endometriotic tissue were the highest in red lesions, intermediate in black and the lowest in white lesions. The expression of HGF and c-Met mRNA stimulated by IL-6 and TNF-α was examined by RT-PCR. We observed the dose-dependent increased expression of both HGF mRNA and c-Met mRNA in stromal cells derived from eutopic endometrium. As a biological effect, HGF significantly proliferated HeLa cells and endometrial stromal cells in bio-cell culture. From these results, it would appear that HGF influences the interaction between epithelium and stroma in endometrium by autocrine and paracrine manner, with resulting growth of endometrial tissue. 4. Influence of macrophage on the growth of endometriosis. It is well known that macrophage accelerates endometrial growth by secreting various cytokines and growth factors. Peritoneal fluid volume and number of macrophage in peritoneal fluid are more abundant in endmetriosis compared with control. We examined the number of macrophages phagocytized beads as activated macrophages, using a flow cytometric assay. The level of phagocytosis in endometriosis was significantly higher than control groups. We also examined the number of macrophage as idenfied by immunoreaction to CD68. Macrophage infiltration significantly increased in red lesions compared with black and white lesions. Macrophage infiltration in eutopic endometrium was higher in endometriosis than control group. Macrophage from peritoneal fluid with endometriosis produced more HGF than control. Expressions of HGF mRNA and c-Met mRNA induced by Lipopolysaccharide (LP S) in macrophage were more stro

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