Recent evidence suggests that oxidative stress is involved in the pathophysiology of preeclampsia. Using immunohistochemistry and Western blotting, we investigated the oxidative stress- and redox-related molecules, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), thioredoxin (TRX) and redox factor-1 (ref-1) in the placenta in preeclampsia, intrauterine growth restriction (IUGR), preeclampsia + IUGR and in normal pregnancy. Using immunohistochemistry, the level of 8-OHdG was significantly higher in IUGR ( P=0.012) or preeclampsia + IUGR (P=0.0021) than in normal pregnancy, while TRX expression was significantly higher in preeclampsia (P=0.045), and ref-1 expression was significantly higher in preeclampsia (P=0.017), IUGR (P=0.016) and preeclampsia + IUGR (P=0.0038) than in normal pregnancy. The levels of 4-HNE did not differ significantly between either preeclampsia or IUGR and normal pregnancy. A significant positive correlation was observed between TRX and ref-1 expressions in both normal (rho=0.52) and complicated (rho=0.43) pregnancies. Using Western blotting, ref-1 expression tended to be higher in complicated pregnancies than in normal pregnancy (P=0.09). These results suggest that oxidative DNA damage is increased in IUGR and that redox function is enhanced in both preeclampsia and IUGR compared with normal pregnancy.
The Wilms' tumor gene WT1 plays multiple roles in the development of the genitourinary organs and Wilms' tumors. The aims of this study were to immunohistochemically evaluate WT1 expression in normal female genital tissues and in epithelial ovarian tumors and to look for correlations between WT1 expression and histologic subtypes and cell proliferation in epithelial ovarian tumors. In normal female genital organs, WT1 expression was recognized in ovarian surface epithelium, the lining of inclusion cysts, and tubal epithelium, but not in the cervical or endometrial epithelium. In epithelial ovarian tumors, serous tumors generally revealed a high WT1 expression. Among adenocarcinomas, serous carcinoma revealed a significantly higher WT1 expression than the other histologic subtypes. There were no significant correlations between the WT1 labeling index and the Ki-67 labeling index, and no significant difference in survival between those showing high and low WT1 expression among the malignant cases. These results suggest that WT1 expression may be related to cell differentiation, and that the histologic subtypes of epithelial ovarian carcinomas may differ considerably in their biological characteristics.
Using the immunohistochemical technique, we investigated the expression of CD10 in normal female genital tissues, chorionic villi and decidua of early gestation, endometriotic lesions, and uterine mesenchymal tumors. The cytoplasm of normal endometrial stromal cells was consistently positive for CD10. During early gestation, decidualized endometrial stromal cells were negative or only focally positive for CD10, whereas nondecidualized stromal cells were diffusely positive. Syncytiotrophoblast was positive for CD10 on the apical surface, whereas chorionic mesenchymal cells were diffusely positive within the cytoplasm. Cytotrophoblast and intermediate trophoblast were negative for CD10. Groups of stromal cells surrounding cervical glands were often positive for CD10. Myometrium, endometrial and cervical glands, cervical squamous epithelia, and tubal epithelia and stroma exhibited no reactivity for CD10. In endometriosis and adenomyosis, ectopic endometrial stromal cells were usually positive for CD10. Endometrial stromal tumors, including undifferentiated uterine sarcomas, mostly showed diffuse immunoreactivity for CD10. Leiomyomas and leiomyosarcomas were negative or focally (< 5% of cells staining) positive (8/12 leiomyomas and 4/8 leiomyosarcomas) for CD10, except for 1 myxoid leiomyosarcoma that showed CD10 staining in the myxoid areas. These data suggest that diffuse CD10 staining is characteristic of normal and neoplastic endometrial stromal cells, unless they are decidualized.
Adenoma malignum of the uterine cervix (mucinous type of minimal deviation adenocarcinoma, mucinous MDA), is a unique neoplasm that is difficult to diagnose owing to the deceptively benign appearance of the tumour cells. The present study was undertaken to explore the phenotypic expression of this tumour compared with those of non-neoplastic cervical tissues and of cervical carcinomas of various types. Ten cases of mucinous MDA, 50 cases with non-neoplastic cervical tissues, 13 of cervical adenocarcinoma including the mucinous (endocervical or intestinal type) and endometrioid types, and 2 of mucoepidermoid carcinoma were examined by various histochemical staining methods, including those for gastric mucins, pepsinogen, lysozyme, chromogranin A and carcinoembryonic antigen. The results revealed that mucinous MDA characteristically exhibited gastric phenotypes. The presence of gastric metaplasia was also demonstrated in 9 cases of mucinous MDA and in 5 of the other cases examined. The 7 endocervical-type adenocarcinomas also included 4 that expressed gastric phenotypes, and 2 of the 3 intestinal-type adenocarcinomas showed the same properties focally. These results indicate the presence of a group of lesions expressing gastric phenotypes in the uterine cervix and suggest a close relationship between these lesions. Cervical adenocarcinomas expressing gastric phenotypes are probably derived from MDA.
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