Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ki-67 is a monoclonal antibody directed against a nuclear antigen present only in proliferating cells. To assess the growth potential of uterine endometrial cancer, the population of cells in proliferating cycle (%PC) was examined with Ki-67, using flow cytometry. The %PC of 27.18 +/- 12.00% in 22 endometrial cancers was significantly higher than the 14.5 +/- 5.94% found in 28 normal endometrial tissues. In premenopausal endometrial tissue, the %PC in the proliferatory phase was significantly higher than the %PC found in the secretory phase. In endometrial cancers, an increase of %PC was found in cases with deep myometrial invasion, and the %PC was elevated in groups containing histologically poorly differentiated types when compared to groups of well-differentiated and moderately differentiated types. Sorted cells reactive with Ki-67 antibody were large and had a high nuclear/cytoplasmic ratio. On the bases of these results, it was concluded that a Ki-67 Ag/DNA dual-color assay would be useful to examine the growth fraction in endometrial carcinoma and that an increased growth fraction was related to deep myometrial invasion or poorly differentiated types.
 ...
PMID:Growth potential of endometrial cancers assessed by a Ki-67 Ag/DNA dual-color flow-cytometric assay. 154 39

The proliferative activity of various parts of normal and malignant endometrium was evaluated using an immunohistochemical approach and flow cytometry (FCM). The two monoclonal antibodies, Ki-67 and anti-DNA polymerase alpha antibody (anti-poly alpha antibody) were used to detect the proliferative activity of cells, and the percentage of the Ki-67 and anti-poly alpha positive cells were measured. Proliferative indices (PI; percentage of S and G2M phase) and DNA ploidy were measured by FCM. Normal endometrial specimens from 29 patients with benign diseases were used and three different parts (fundus, middle, and low part of the uterus) were examined. In the proliferative phase of normal endometrium, there was no significant difference in the proliferative activity in the three parts. In 20 patients with endometrial carcinomas with myometrial invasion, tissues were taken from the myometrial invasive site and the central part of the tumor tissue. In the cases of endometrial carcinoma, the myometrial invasive site had a higher proliferative activity than central part of the tissue. The proliferative activity measured by the immunohistochemistry was correlated with the histological grade of malignancy, but it was not consistent with PI by FCM. This suggests that the proliferative activity measured by the immunohistochemistry is independent of flow cytometric PI.
 ...
PMID:Proliferative activity in normal endometrium and endometrial carcinoma measured by immunohistochemistry using Ki-67 and anti-DNA polymerase alpha antibody, and by flow cytometry. 157 57

We previously reported that recombinant interferon-gamma (IFN-gamma) induces HLA-DR (human lymphocyte antigen) molecules of the major histocompatibility complex in human endometrial epithelial cells in vitro. We now report that IFN-gamma inhibits the proliferation of human endometrial epithelial cells and a human endometrial carcinoma cell line (EnCa101AE). Human endometrial epithelial cells expressed HLA-DR molecules and underwent morphological changes when exposed to IFN. Furthermore, the proliferation of these cells, as evidenced by nuclear labeling of bromodeoxyuridine (an analog of thymidine that is incorporated into cells in S phase), was markedly reduced, in a dose-dependent manner, by IFN-gamma. IFN-gamma induced HLA-DR expression, morphological changes, shedding from the substratum, and cell death in EnCa101AE cells. In addition, cell number and the numbers of bromodeoxyuridine-, Ki-67 (a nuclear marker of proliferation)-, and MPM-2 (a marker of mitotic cells)-positive cells were markedly lower in the EnCa101AE cultures treated with IFN-gamma than those in control cultures. The cytostatic and HLA-DR-inducing effects of IFN-gamma could be abrogated by neutralization with a polyclonal antibody, and IFN-gamma effects were reversible within days after its withdrawal. These findings indicate that IFN-gamma inhibits proliferation of human endometrial epithelial cells and suggest that this factor may locally regulate the proliferation of these epithelial cells in vivo.
 ...
PMID:Antiproliferative effect of interferon-gamma in human endometrial epithelial cells in vitro: potential local growth modulatory role in endometrium. 245 43

In order to clarify the factors that affect growth of endometrial carcinoma, immunohistochemical analyses of bcl-2, p53, sex steroid receptors, and Ki-67 were performed in 35 cases of endometrial carcinoma (32 endometrioid and three clear-cell carcinomas). Correlation of antigen expression with clinicopathological features was analyzed. Expression of bcl-2 was found in 58.8, 33.3, and 20.0% of grade 1 (G1), grade 2 (G2), and grade 3 (G3) endometrial carcinomas, respectively. Estrogen receptor (ER) was observed in 70.6, 22.2, and 0% of G1, G2, and G3 cases (p < 0.01), respectively. In contrast, expression of p53 was found in 5.8, 33.3, and 60.0% of G1, G2, and G3 cases, respectively. The labeling index of Ki-67 correlated with p53 overexpression (p < 0.01). Lymph node metastases were observed in 6.6 and 5.5% of ER- and PR (progesterone receptor)-positive carcinomas, whereas metastases were observed in 44.4 and 53.3% of ER- and PR-negative carcinomas, respectively (p < 0.05). Lymph node metastases were observed in 50.0% of p53-positive carcinomas, whereas metastases were observed in 22.2% of p53-negative carcinomas (p < 0.05). These results suggest that bcl-2 expression in endometrial carcinomas is regulated in a hormone-dependent manner. Expression of bcl-2 may occur more frequently in estrogen-related, low-grade endometrial carcinomas, whereas p53 overexpression is found more often in endometrial carcinomas in estrogen-unrelated, high-grade endometrial carcinomas with prominent proliferative activity and a high frequency of lymph node metastases.
 ...
PMID:Immunohistochemical analysis of endometrial adenocarcinoma for bcl-2 and p53 in relation to expression of sex steroid receptor and proliferative activity. 881 80

To clarify whether changes in bcl-2 protein (bcl-2) expression are directly linked to differentiation, an immunohistochemical investigation was carried out on areas of squamous differentiation within 38 endometrial carcinomas (25 grade 1 and 13 grade 2 cases) as well as eight grade 1 carcinomas after progesterone therapy. Such areas of altered differentiation were subdivided into foci of squamous metaplasia (Sq-M) and morules. Expression of oestrogen and progesterone receptors (ER and PR) and cell proliferation were also examined. Immunoreactivity scores for bcl-2 in Sq-M foci were significantly lower than in the surrounding tumour regions, in line with reduced staining for ER and PR and Ki-67 labelling indices (LIs), while morule values were intermediate. After progesterone therapy, a marked decrease in bcl-2 immunoreactivity was found in the response group, along with low Ki-67 LIs and tumour cell maturation. These results indicate that in endometrial carcinoma, down-regulation of bcl-2 expression may be closely linked with squamous differentiation, in line with changes in ER and PR expression, as well as in cell proliferation. In addition, bcl-2 expression appears to be down-regulated by progesterone therapy through tumour cell maturation, indicating that bcl-2 may be a clinically useful marker of hormone therapy effects.
 ...
PMID:Down-regulation of bcl-2 expression is closely related to squamous differentiation and progesterone therapy in endometrial carcinomas. 930 64

Clinicopathological, immunohistochemical and molecular genetic analyses of endometrial carcinoma suggest different pathogenetic pathways for endometrioid and serous carcinoma. Most endometrioid carcinomas are associated with endometrial hyperplasia, are ER/PR positive, p53 negative and express low Ki-67. In contrast, almost all serous carcinomas develop from endometrial intraepithelial carcinoma (EIC) in a background of atrophy. These tumors are ER/PR negative, strongly express p53 and show high Ki-67 labeling. On the molecular genetic level, 25-30% of endometrioid carcinomas show microsatellite instability (MI), 25-30% harbor mutant K-ras and less than 10% have mutant p53. In contrast, more than 90% of serous carcinomas have p53 mutations, 2% K-ras mutations and none MI. Among endometrioid carcinomas, K-ras mutations occur most frequently in FIGO grade 2 and 3 tumors and p53 mutations in FIGO grade 3 tumors. In contrast, MI is equally distributed among all FIGO grades. These findings support the view that endometrioid carcinoma develops slowly in a progressive fashion from endometrial hyperplasia. Mutation of p53 occurs late in tumor progression. Thus, endometrioid carcinogenesis resembles the proposed model for colorectal carcinogenesis. In contrast, serous carcinoma develops rapidly from EIC in a background of atrophy. Mutation of p53 occurs early in serous carcinogenesis and this may account for the highly aggressive behavior of this tumor.
 ...
PMID:A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. 947 74

Cyclin dependent kinases (cdks) and cyclins regulate the progression of cells through the cell cycle and can be overexpressed in human cancers. The purpose of this study was to evaluate the immunohistochemical profile of these proliferation-associated proteins and correlate the results with clinicopathologic parameters of endometrial carcinomas. Archival tissue sections from 91 endometrial carcinomas were immunostained using monoclonal antibodies against p34CDC2 cdk, cyclins A and B1, p120, Ki-67, and PCNA. Immunoreactivity was semiquantitatively assessed and the results correlated with pathologic features and survival. Of the 91 endometrial carcinomas, 74 were endometrioid (17 villoglandular, 57 of usual type) and 17 were papillary serous carcinomas. The positivity rates for the different proteins in papillary serous and endometrioid tumors, respectively, were as follows: p34CDC2, 24% and 23%; cyclin A, 71% and 64%; cyclin B1, 24% and 26%; p120, 47% and 9%; Ki-67, 82% and 64%; and PCNA, 47% and 47%. Only p120 correlated with histologic tumor type with significantly higher expression in both papillary serous and villoglandular endometrioid carcinomas compared to nonvilloglandular endometrioid carcinomas (p = 0.0001). p120 positivity also correlated with advanced tumor stage (p = 0.0001). Ki-67, cyclin A, and PCNA correlated with patient survival in endometrioid carcinomas on univariate analysis (p = 0.01, 0.02, and 0.003, respectively), but, on multivariate analysis, only tumor grade (p = 0.02) and depth of invasion (p = 0.04) were independent predictors of outcome. In summary, although most of the cell proliferation-associated proteins studied did not appear to be associated with clinicopathologic features of endometrial carcinoma, there was significantly higher expression of p120 in papillary serous and villoglandular endometrioid carcinomas compared to nonvilloglandular endometrioid carcinomas, suggesting a possible role of p120 in tumor behavior. In addition, Ki-67, cyclin A, and PCNA expression correlated with survival in endometrioid carcinoma, but only in a univariate analysis.
 ...
PMID:Cell proliferation-associated proteins in endometrial carcinomas, including papillary serous and endometrioid subtypes. 978 32

For patients with localized endometrial carcinoma at primary operation, there is a definite need for more specific prognostic parameters to select patients for adjuvant therapy. The purpose of this study was to evaluate the applicability and prognostic significance of markers for tumor cell proliferation (S phase fraction and Ki-67 expression) among endometrial carcinoma patients, relative to the information derived from established clinicopathological variables including DNA and receptor analyses. In a prospective study of 115 patients treated for endometrial carcinoma, fresh tumor tissue was collected for assessments of ploidy, S phase fraction and hormone receptor concentrations. Ki-67 expression was assessed immunohistochemically on sections from formalin-fixed and paraffin-embedded tumor specimens. These variables were examined together with traditional clinicopathological features in univariate and multivariate (Cox proportional hazards regression model) survival analyses. The median follow-up time for the survivors was 9 years (range, 5-15), with no patient lost due to insufficient follow-up information. The expression of Ki-67 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.0004), histological type (P = 0.03), and histological grade (P = 0.0001). S phase fraction was significantly associated with histological grade (P = 0.02), whereas the association with histological type was of borderline significance (P = 0.07). In univariate analyses, survival was significantly influenced by FIGO stage (P <0.0001), histological type (P = 0.0002), histological grade (P = 0.002), ploidy (P = 0.015), S phase fraction (P = 0.017), progesterone receptor concentration (P = 0.02), and Ki-67 expression (P <0.0001). In Cox regression analysis, FIGO stage (hazard ratio, 11.7; 95% confidence interval, 4.3-32.1) and Ki-67 (hazard ratio, 8.7; 95% confidence interval, 3.0-25.2) were the only variables with independent prognostic impact. When patients whose tumors were confined to the uterus were analyzed separately, Ki-67 was the only variable with an independent prognostic importance. Ki-67 expression was superior to S phase fraction both in applicability and prognostic value. FIGO stage and Ki-67 expression were the only variables with independent prognostic impact in Cox regression analysis. Ki-67 expression is assessed on the histological specimens taken routinely, with no separate sampling technique; this should make it easy to use in a routine setting.
 ...
PMID:Identification of high-risk patients by assessment of nuclear Ki-67 expression in a prospective study of endometrial carcinomas. 982 42

In normal human endometrium, expressions of the proto-oncogenes c-fos and c-jun parallel. We have previously shown that the expression of c-jun is related to proliferation and estrogen receptor (ER) status in endometrial epithelial cells. In this study, we analyzed endometrial cancer tissues for c-fos and c-jun messenger RNA (mRNA) expression by Northern blotting. Proto-oncogene expression was compared with ER and progesterone receptor (PR) status and with the proliferation marker Ki-67, as well as with histological grade and the use of hormone-replacement therapy (HRT). Messenger RNA for c-fos was detected in 35 of 37 cancer tissues and mRNA for c-jun in 37 of 40 tissue samples studied. No correlation was observed between the relative mRNA levels of c-fos and c-jun, suggesting distinct control mechanisms, if any, in endometrial cancer. In contrast to normal endometrium, there was no correlation between the proto-oncogene expression and Ki-67, ER or PR immunoreactivity. Neither were there any correlations between c-fos or c-jun expression and the histological grade of the tumor or preceding HRT. Our results reveal the loss of association between proto-oncogene expression and ovarian steroid receptors or cell proliferation in malignant endometrium. This gives further support to the hypothesis that alterations in estrogen and progesterone signalling pathways are involved in the pathogenesis of endometrial cancer.
 ...
PMID:The association between c-fos and c-jun expression and estrogen and progesterone receptors is lost in human endometrial cancer. 1039 30

Traditional prognostic factors often fail to identify a subgroup of endometrial carcinoma (EC) patients with an apparently paradoxical poor outcome. We therefore analyzed tumor cell proliferation immunohistochemically in a series of 164 endometrial carcinomas (EC) and compared its prognostic impact with that of the standard prognostic factors patient age, FIGO stage, FIGO grading, and histopathologic subtype. In addition to the established proliferation markers Ki-S5 (Ki-67) and KiS4 (topoisomerase IIalpha), we used a novel monoclonal antibody (MAb), anti-repp 86, which binds to a recently described proliferation-specific protein (p86) expressed exclusively in the S, G2, and M phases of the cell cycle. anti-repp 86, Ki-S4, and Ki-S5 immunoreactive labeling indices (LI) correlated significantly with FIGO stage, FIGO grade, and myometrial invasion, but not with histopathologic subtype. By univariate analysis, conventional prognostic factors and proliferation indices were all predictive of disease-related mortality. A multivariate Cox regression analysis selected anti-repp 86 LI (P = .002), FIGO stage (P = .02), and histopathologic type as significant prognosticators of recurrence; anti-repp 86 LI (P = .001) and histopathologic type (P = .0106) also emerged as relevant predictors of mortality. A hierarchical forward regression model with the conventional prognosticators entered first and with anti-repp 86 entered next showed that anti-repp 86 and histopathologic subtype were the superior independent prognostic indicators for an increased risk of recurrence and cancer-related death. We conclude that the evaluation of anti-repp 86 immunostaining is an easily performable and exceptionally reliable method for identifying EC patients with adverse prognosis.
 ...
PMID:Prognostic significance of a novel proliferation marker, anti-repp 86, for endometrial carcinoma: a multivariate study. 1045 8


1 2 3 4 5 6 7 8 9 Next >>