UMLS:C0476089 - FACTA Search

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Query: UMLS:C0476089 (endometrial cancer)
11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ovarian hormones are considered to be capable of regulating expression of beta-catenins. A possible role of beta-catenin in alteration of cell morphology has been proposed, but little is known about beta-catenin expression during changes in the tumor morphology of endometrial carcinomas induced by progesterone therapy. To clarify changes in expression of beta-catenin and their relation to morphological alteration, expression of hormone receptors and several cell kinetic markers, sequential biopsy and hysterectomy specimens of 23 endometrial carcinoma and 6 complex hyperplasia with atypia (atypical hyperplasia) cases receiving progesterone therapy were investigated. In vitro assay was also conducted using two endometrial carcinoma cell lines (HEC265 and Ishikawa) expressing progesterone receptors (PRs). An increase of nuclear beta-catenin accumulation was evident during progesterone therapy in endometrial carcinomas and atypical hyperplasias. The nuclear labeling indices were significantly associated with gene mutations and alteration in morphological features in response to progesterone, independently of the status of Ki-67, p21WAF1 and p27Kip1, and hormone receptors. In HEC265 having a beta-catenin gene mutation (A32V), cytoplasmic beta-catenin levels were elevated by progesterone treatment, linked to down-regulation of PR expression, but such changes were relatively minor in Ishikawa without the gene alterations. These findings demonstrate a possible role of progesterone in regulation of beta-catenin expression in endometrial tumors. Moreover, nuclear beta-catenin accumulation, like gene abnormalities, is associated with the alteration of tumor morphology due to progesterone, indicating that beta-catenin may be a clinically useful marker of hormone therapeutic effects.
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PMID:Up-regulation and nuclear localization of beta-catenin in endometrial carcinoma in response to progesterone therapy. 1270 83

Although aberrant expression of several cell-cycle regulators has been reported in endometrial carcinoma, correlations among these factors and their prognostic significance have not fully been elucidated. In the present study, expression of cyclins (D1, E, A, and B1), cyclin-dependent kinases (cdk2, cdk4, and cdc2), and tumor-suppressor gene products (p53, p21, and p27) were systematically examined by immunohistochemistry in 82 cases of endometrial carcinoma and 20 normal endometria. Results were compared with the expression of Ki-67, sex steroid receptor status, clinicopathological parameters, and patient outcomes. Positive staining for cyclin D1, cyclin E, cyclin A, cyclin B1, cdk2, cdk4, cdc2, p53, p21, and p27 was observed in 63%, 66%, 31%, 32%, 51%, 77%, 71%, 43%, 35%, and 60% of the 82 carcinomas, respectively. Among these factors, positive staining for cyclin D1, cdk4, and p53 was significantly frequent in advanced-stage tumors, and that for cyclin D1, cyclin A, cdk4, p21, and p53 was more frequent in higher-grade tumors. High correlation was found between cyclin A and p53 expression, between cyclin D1 and cdk4 expression, between cdk4 and Ki-67 expression, and between p21 and Ki-67 expression. Multivariate analysis showed that the factors for poor prognosis were advanced stage and cyclin A positivity. These findings suggest that various cell-cycle regulators are involved in activated cell growth of endometrial carcinoma, and that positive staining for cyclin A could be a useful marker for unfavorable patient prognosis.
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PMID:Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor-suppressor gene products, Ki-67, and sex steroid receptors in endometrial carcinoma: positive staining for cyclin A as a poor prognostic indicator. 1279 21

The prognostic significance of the invasive type of carcinoma cells in endometrial carcinoma is not defined. We evaluated the prognostic significance of the invasive type, as well as the immunostains of p53, c-erbB-2, Ki-67 antigen and MDM2 in endometrial endometrioid adenocarcinoma. This prospective analysis comprised 112 patients with endometrioid adenocarcinoma of the uterine corpus who had undergone surgery and were traced for more than 5 years after the operation. They were divided into recurrence (16 patients) and non-recurrence (96 patients) groups. The invasive type of carcinoma cells was divided into expansile, mixed (expansile and infiltrative) and infiltrative pattern. The difference in the invasive type (P < 0.001) and p53 expression (P = 0.004) between the recurrence and non-recurrence groups was significant in the univariate analysis. Moreover, the invasive type was significant in the multivariate analysis (P = 0.004). In contrast, the difference in MDM2 expression, c-erbB-2 expression and the Ki-67 labeling index in both groups was not significant in the univariate analysis. The infiltrative pattern of the invasive type (P < 0.001) and p53 expression (P = 0.043) were significantly related to a poor prognosis in the Kaplan-Meier method using the log-rank test. In conclusion, the current study indicated that the infiltrative pattern of the carcinoma cells is a predictor for poor prognosis in endometrioid adenocarcinoma in the uterine corpus. It was also indicated that p53 immunostains are useful as a predictor, but Ki-67 antigen, c-erbB-2 and MDM2 stains are not.
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PMID:Prognostic significance of the infiltrative pattern invasion in endometrioid adenocarcinoma of the endometrium. 1289 27

Two types of endometrial carcinoma can be distinguished: type I tumours, which are oestrogen-related and are typically low-grade endometrioid carcinomas; and type II tumours, which are unrelated to oestrogen stimulation and are often non-endometrioid carcinomas. The molecular abnormalities involved in carcinogenesis appear to be different for these tumour types. The aim of this study was to test the hypothesis that an abnormality in the Wnt/beta-catenin signalling pathway is a molecular feature of type I endometrial carcinoma. This study investigated nuclear beta-catenin by immunohistochemistry in 233 endometrial carcinomas and analysed its correlation with several immunohistochemical, histological, and clinical parameters, such as proliferation rate (Ki-67), expression of oestrogen and progesterone receptors, and survival. Nuclear beta-catenin expression was observed in 39 cases (16%). All tumours expressing nuclear beta-catenin were endometrioid adenocarcinomas, were significantly better differentiated, and were more often hormone receptor-positive than tumours without nuclear beta-catenin. No correlation with proliferation rate was found. It was found that several features of type I endometrial carcinoma occur significantly more often in tumours expressing nuclear beta-catenin, suggesting that an abnormality in the Wnt/beta-catenin signalling pathway, resulting in nuclear beta-catenin immunopositivity, is a molecular feature of a subset of type I endometrial carcinomas.
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PMID:Nuclear beta-catenin is a molecular feature of type I endometrial carcinoma. 1509 79

Fluorescence in situ hybridization (FISH) is the most widely used technique to detect HER-2/neu gene amplification; however, it is only available in some institutions. In contrast, chromogenic in situ hybridization (CISH) can be evaluated by routine light microscopy. In endometrial carcinoma there are few data concerning HER-2/neu status and prognosis. Therefore, we determined HER-2/neu gene status by CISH using a digoxigenin-labelled probe on 60 formalin-fixed paraffin-embedded endometrial carcinomas. The data were compared with the immunohistochemistry of HER-2/neu (A0485, TAB250), p53, Ki-67, clinicopathological factors, and survival. By conventional light microscopy, HER-2/neu amplification (>/=6 copies >50% cancer cells) was detected in 14% (8/59) tumours, HER-2/neu overexpression (>10% cells moderate/strong complete membrane staining) in 22% (13/60) for A0485, and 18% (11/60) for TAB250, p53 (>10% +cells) in 61% (36/59), and Ki-67 (>50% +cells) in 50% (30/60). Discordant cases for CISH and immunohistochemistry, as well as all (2+) were further analysed by FISH (Vysis). Among 10 cases (2+) and not amplified by CISH, two showed low-level amplification by FISH. Significant correlation was found between amplification and protein overexpression (P</=0.001), and a trend with nonendometrioid type, higher grade, and older age. A better outcome (Kaplan-Meier) was observed for patients with nonamplified (1-5 copies per nucleus) or low-level (6-10 copies) amplification tumours, low Ki-67 expression, age <50 years, endometrioid type, low FIGO (International Federation of Obstetrics and Gynaecology) grade and stage, superficial myometrial infiltration, and no lymph-vascular invasion (P</=0.036), but only as a trend for HER-2/neu protein negative (P=0.13). Cox analysis revealed age, FIGO grade and stage, myometrial infiltration, and lymph-vascular invasion to be independent prognostic factors (P</=0.05), and a trend for HER-2/neu gene copy number (0.18). In endometrial carcinoma, HER-2/neu gene status can be readily assessed by CISH in routine clinical practice, and it gives more prognostic information than HER-2/neu by immunohistochemistry. FISH analysis in (2+) cases but negative by CISH may detect additional tumours with low-level amplification.
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PMID:Analysis of HER-2/neu amplification in endometrial carcinoma by chromogenic in situ hybridization. Correlation with fluorescence in situ hybridization, HER-2/neu, p53 and Ki-67 protein expression, and outcome. 1475 23

The functional consequences of up-regulation of beta-catenin as a transcription factor are complex in different tumors. To clarify roles during squamous differentiation (SqD) of endometrial carcinoma (Em Ca) cells, we investigated expression of beta-catenin, as well as cyclin D1, p53, p21WAF1, and PML (promyelocytic leukemia) in 80 cases of Em Ca with SqD areas, in comparison with cell proliferation determined with reference to Ki-67 antigen positivity. The impact of beta-catenin-T-cell factor (TCF)-mediated transcription was also examined using Em Ca cells. In clinical cases, nuclear beta-catenin accumulation was more frequent in SqD areas, being positively linked with expression of cyclin D1, p53, and p21WAF1, and inversely with Ki-67 and PML immunoreactivity. Significant correlations of nuclear beta-catenin, cyclin D1, p53, and p21WAF1 were noted between SqD and the surrounding carcinoma lesions. The Ishikawa cell line, with stable or tetracycline-regulated expression of mutant beta-catenin, showed an increase in expression levels of cyclin D1, p14ARF, p53, and p21WAF1 but not PML, and activation of beta-catenin-TCF4-mediated transcription determined with TOP/FOP constructs. The cell morphology was senescence-like rather than squamoid in appearance. Moreover, overexpressed beta-catenin could activate transcription from p14ARF and cyclin D1 promoters, in a TCF4-dependent manner. These findings indicate that in Em Cas, nuclear beta-catenin can simultaneously induce activation of the p53-p21WAF1 pathway and overexpression of cyclin D1, leading to suppression of cell proliferation or induction of cell senescence. However, overexpression of beta-catenin alone is not sufficient for development of a squamoid phenotype in Em Ca cells, suggesting that nuclear accumulation is an initial signal for trans-differentiation.
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PMID:Beta-catenin simultaneously induces activation of the p53-p21WAF1 pathway and overexpression of cyclin D1 during squamous differentiation of endometrial carcinoma cells. 1511 20

Tamoxifen and raloxifene are widely used in clinical practice. It has been found that tamoxifen treatment increases the risk of development of endometrial cancer. The effects of tamoxifen and raloxifene on endometrium might be caused by different estrogen receptor expression. The aim of the present study was immunohistochemical evaluation of the effects of tamoxifen and raloxifene on estrogen receptors, and Ki-67 antigen expression in the human endometrial adenocarcinoma Ishikawa cell line. Tamoxifen in concentrations of 10 microM and 20 microM increased ERalpha expression without any effect on ERbeta. All used concentrations of tamoxifen and raloxifene (0.1 nM, 1 nM, 10 nM, 1 micro M, 10 microM and 20 microM) had no effect on expression of ERbeta. Tamoxifen, but not raloxifene, increased Ki-67 antigen expression in the Ishikawa cell line. Tamoxifen, in contrast to raloxifene, increased proliferation of endometrial adenocarcinoma cells as well as exerted the shift of ERalpha/ERbeta ratio. Thus, it could be responsible for increased carcinogenic effect during tamoxifen treatment.
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PMID:Differential effects of raloxifene and tamoxifen on the expression of estrogen receptors and antigen Ki-67 in human endometrial adenocarcinoma cell line. 1528 30

We determined the effects of several non-steroidal anti-inflammatory drugs (NSAIDs), aspirin (acetylsalicylic acid, ASA), indomethacin and a cyclooxygenase-2 (COX-2)-selective inhibitor (NS398), on cellular proliferation and regulation of COX-2 protein expression in endometrial cancer cells in vitro, and investigated their modes of action. All three NSAIDs markedly inhibited the proliferation of Ishikawa, HEC-1A and AN3CA endometrial cancer cell lines in a time- and concentration-dependent manner. ASA and indomethacin triggered apoptosis in cells of all three lines through release of cytosolic cytochrome c, activation of caspase-9 and-3, and cleavage of poly(ADP-ribose) polymerase (PARP), but NS398 induced minimal apoptosis only in Ishikawa cells. ASA altered the cell cycle distribution, with G2/M phase accumulation of cells, and induced overexpression of Ki-67 protein. Both ASA and indomethacin reduced the protein levels of Bcl-2 and Bcl-xl, but upregulated those of Bax and Bcl-xs. COX-2 protein expression and PGE(2) production were upregulated by ASA and indomethacin in all three cell lines. However, NS398 did not alter COX-2 protein expression or PGE(2) production in these cells. These results indicate that NSAIDs inhibit proliferation of endometrial cancer cells independently of the reduction of COX-2 protein expression. A cytochrome c-dependent apoptotic pathway and/or cell cycle arrest may contribute to the inhibitory effects of these NSAIDs.
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PMID:Non-steroidal anti-inflammatory drugs inhibit cellular proliferation and upregulate cyclooxygenase-2 protein expression in endometrial cancer cells. 1554 8

PTEN and the PI3K/Akt pathway are involved in the development and/or progression of endometrial carcinoma. To clarify the impact of the pathway-related molecules on prognosis, we analyzed PTEN, phosphorylated-Akt (p-Akt), and Ki-67 expression by immunohistochemistry in 99 patients with advanced endometrial carcinoma. PTEN-negative or PTEN-mixed staining was found in 66% of tumors. Positive staining of p-Akt was found in 40% of tumors. Loss of PTEN expression (negative or mixed) was significantly associated with positive p-Akt expression. The patients with PTEN-positive and p-Akt-negative expression clearly showed a higher survival rate than patients in the other groups. Subsequent multivariate analysis revealed that the combination of PTEN/Akt expression was an independent prognostic factor. Examining the relationship between p-Akt expression and Ki-67 labeling index (LI), we found that negative p-Akt was related to a decrease in Ki-67 LI. Additionally, the patients with low Ki-67 LI, as determined by p-Akt-expression status, had a better prognosis. In the present study, we demonstrated that PTEN-positive and p-Akt-negative expression was a predictor of survival for patients with advanced endometrial carcinoma. This study suggests the clinical significance of PTEN and p-Akt expression analysis in treatment decisions for patients with advanced endometrial carcinoma.
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PMID:PTEN-positive and phosphorylated-Akt-negative expression is a predictor of survival for patients with advanced endometrial carcinoma. 1601 20

To further elucidate the significance of p53 mutation in endometrial carcinoma, we investigated it in endometrioid-type endometrial carcinomas showing intratumoral heterogeneous p53 expression. In addition, we also examined the correlation of p53 mutation and cyclin A expression, because we previously reported a topological correlation between the expression of p53 and cyclin A. The p53 mutation in exons 5-8 in 54 cases of endometrial carcinoma showing immunohistochemical expression of p53 was examined using microdissected tissue DNAs. Of the 54 p53-positive endometrial carcinomas, 23 (43%) had p53 mutation with a tendency in histologically higher grade tumors. Ten of the 54 showed a heterogeneous p53 expression, and in 9 of the 10 cases, p53 mutation was present only in p53-positive sites, which were often found in histologically less differentiated areas with elevated Ki-67 in the same tumor. Cyclin A expression was topologically observed in p53-positive areas; however, it was noted in both tumors with (12/23, 52%) and without (18/31, 58%) p53 mutation. These results suggest that p53 mutation is a late event and plays an important role in the acquisition of malignant potentials in endometrioid-type endometrial adenocarcinomas. Unexpectedly, accumulation of the p53 protein itself may be important in cyclin A overexpression.
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PMID:Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas. 1602 9

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