Expression of replication-licensing factors MCM2 and MCM3 in normal, hyperplastic, and carcinomatous endometrium: correlation with expression of Ki-67 and estrogen and progesterone receptors.

Minichromosome maintenance (MCM) proteins are essential for cell cycling due to their function as replication-licensing factors. The aim of the present study was to investigate the clinicopathologic implications of the MCM2 and MCM3 in endometrial carcinogenesis. The authors investigated the immunohistochemical expression of MCM2 and MCM3, Ki-67, estrogen receptor, and progesterone receptor in 23 normal endometria, 9 endometrial hyperplasias, and 60 endometrial carcinomas. In the normal endometrial glands, the expression of MCM2 and MCM3 was significantly higher in the proliferative phase than in the secretory phase and was strongly correlated with Ki-67 expression. Similar correlation between the expression of MCMs and Ki-67 was also found in endometrial hyperplasia. In endometrial carcinomas, however, the expression of MCM2 and MCM3 was significantly lower than that in the normal proliferative endometrium. There was only a weak correlation between MCM2 and Ki-67, and no significant correlation between MCM3 and Ki-67 expression. These findings suggest that the expression of MCM2 and MCM3 directly reflects cell proliferation in normal and hyperplastic endometria. In endometrial carcinomas, however, there is a discrepancy between the expression of MCMs and cell proliferation, suggesting that the replication-licensing system may be aberrant in endometrial carcinomas.

Toward understanding the natural history of ovarian carcinoma development: a clinicopathological approach.

OBJECTIVE: The natural history of the development of ovarian carcinoma is not known. It also remains undetermined whether ovarian carcinomas develop from benign and/or borderline malignant tumors or arise de novo from the ovarian surface epithelium. METHODS: To address these issues clinicopathologically, we reviewed the clinical charts of 543 patients with epithelial ovarian carcinoma and 252 patients with borderline tumors who underwent laparotomy at seven hospitals and collected patients whose clinical and transvaginal ultrasonography (USG) findings for adnexal regions 12 months or fewer prior to the surgery were available. Histological slides of the resected specimens were reexamined concerning the diagnosis and histological grade, as well as the presence or absence of benign- or borderline-like lesions adjacent to the carcinoma. RESULTS: Forty-nine patients had had gynecological examination with transvaginal USG 12 months or fewer prior to laparotomy. Among them, 35 had carcinomas (11 serous, 6 mucinous, 8 clear cell, 10 endometrioid) and 14 had borderline tumors (8 serous, 6 mucinous). Of the 35 patients with carcinoma, 19 (54%) had been followed up for benign-appearing cysts or endometriotic cysts. In these cases, serial USG examinations revealed an increase in size and/or appearance of the solid part of the cyst. In the remaining 16 (46%), however, there had been no apparent abnormalities in USG, and such cases occurred most frequently for serous carcinomas. CONCLUSIONS: Our findings suggest that approximately half of ovarian carcinomas develop secondarily from preexisting, benign-appearing cysts or endometriotic cysts, whereas the remaining half seem to develop suddenly from a normal-appearing ovary. This appears to be consistent with two possible pathways of ovarian carcinoma development; adenoma-carcinoma sequence and de novo carcinogenesis.

CD10 is a marker for normal and neoplastic endometrial stromal cells.

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.

Hypoxia-induced changes in the expression of VEGF, HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells.

BACKGROUND: Hypoxia is important in cancer progression, and at the stage of detachment of the cancer cells from the primary lesion. This study was undertaken to analyze the effect of hypoxia on angiogenesis and cell proliferation in ovarian cancer. MATERIALS AND METHODS: We first used immunohistochemistry to examine the expression of VEGF in 42 cases of ovarian carcinoma, with relevance to the p53 expression. Then, the expression of VEGF, HIF-1 alpha, cell cycle-related molecules and cell numbers were examined in 4 ovarian cancer cell lines with various p53 gene status. RESULTS: Immunohistochemistry showed that there was no significant correlation between VEGF and p53 expression. Moreover, hypoxia increased the expression of VEGF via up-regulation of HIF-1 alpha irrespective of p53 gene status. However hypoxia did not change the cell numbers, but influenced the expression of cell cycle-related molecules (increased p27 and decreased cyclin D1 and Rb). CONCLUSION: Hypoxia increased VEGF expression in ovarian cancer cells irrespective of p53 gene status.