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

A total of 103 endometrial carcinomas (endometrioid type), as well as 15 samples of normal (atrophic or proliferative phase) and 26 of hyperplastic endometrium, were immunohistochemically investigated for expression of Bcl-2, and oestrogen and progesterone receptors (ER and PR), and the results compared with findings for apoptosis and cell proliferation. Carcinoma cases were subdivided into tubular and solid components on the basis of tumour growth patterns. Immunopositivity for Bcl-2, ER, and PR in tubular components was significantly higher than in the solid category, being negatively associated with histological grading. Immunoreactivity scores revealed that Bcl-2 in the tubular group was positively correlated with PR but not ER, while its expression in normal and hyperplastic endometrium was closely linked with both. Apoptotic and mitotic indices (AI and MI) were both significantly lower in tubular than in solid areas. In the tubular areas, AI, values were significantly lower in the subgroup with a high level of Bcl-2 expression than in either low-level or negative groups. These results indicate that Bcl-2 expression may play a central role in the inhibition of apoptosis in endometrial carcinoma, in particular those cases with tubular components, possibly being associated with PR rather than ER. Changes in the propensity for apoptosis may be related to alterations of tumour growth pattern and of features of differentiation.
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PMID:Bcl-2 expression is correlated with a low apoptotic index and associated with progesterone receptor immunoreactivity in endometrial carcinomas. 895 5

Bcl-2 protein inhibits apoptosis, reduces the requirement for growth factors, and thereby extends the survival of cells. Recent findings of Bcl-2 in several solid tumors suggest that it might contribute to the genesis of some types of cancer. Over-expression of Bcl-2 might play a role in carcinogenesis and malignant progression of endometrial carcinoma. The aims of this study were to determine Bcl-2 expression in endometrial carcinoma in relation to other histopathologic prognostic factors, and to test its prognostic significance in patients with endometrial carcinoma. A total of 61 endometrioid-type endometrial carcinomas were immunohistochemically investigated for Bcl-2 expression on cryostat sections. Bcl-2 localization was observed in cytoplasm in 18 tumors, in nucleus in 27 tumors, or in both in 5 tumors. In 11 tumors, Bcl-2 was observed neither in cytoplasm nor in nucleus. There was not a statistically significant relationship between grade of tumor and Bcl-2 expression. Cytoplasmic Bcl-2 became less frequently expressed as the tumor invaded the myometrium deeper (p < 0.025). Retroperitoneal lymph-node dissection was performed in 57 patients. Multiple-regression analysis showed that lymph-vascular space invasion and nuclear expression of Bcl-2 were correlated to pelvic lymph-node metastasis (p < 0.0001 and < 0.05 respectively). Univariate Cox regression analysis revealed that nuclear Bcl-2 expression was associated with shorter survival (p < 0.05) than that of patients with cytoplasmic Bcl-2 expression. Pelvic node metastasis was a significant prognostic factor for patients who underwent systematic retroperitoneal lymph-node dissection. Cox multivariate-regression analysis revealed that pelvic node metastasis and cervical invasion were the most important prognostic factors in this series of patients. When the analysis was made after exclusion of pelvic node metastasis, histologic grade (hazard ratio = 2.4), cervical invasion (hazard ratio = 3.7) and nuclear Bcl-2 expression (hazard ratio = 11.5) were shown to be significant predictors of survival of the patients. These results indicate that aberrant Bcl-2 expression might be involved in malignant progression of endometrioid-type endometrial carcinoma. Site of Bcl-2 localization may be an important predictor of prognosis for patients with endometrioid-type endometrial carcinoma.
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PMID:Bcl-2 expression and prognosis of patients with endometrial carcinoma. 958 30

To investigate the role of the apoptosis-related genes, Bcl-2, Bax and Survivin genes were analyzed. For the Bax gene, abnormality was detected in 1 of 7 cervical and 1 of 6 endometrial cancer cell lines, 1 of 25 cervical cancer tissues and none of 17 endometrial cancer tissues using PCR-SSCP. In 4 cervical and 2 endometrial cancer cell lines, the ratio of Bcl-2 to Bax expression was higher than the control ratio using Western blotting. Survivin mRNA was detectable in all cell lines and all cancer tissues. The data suggested that these apoptosis-related genes may play important roles in the pathway of carcinogenesis of human uterine cancer.
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PMID:Analysis of Bcl-2, Bax and Survivin genes in uterine cancer. 1037 6

Papillary serous endometrial carcinoma is an aggressive tumor characterized by late-stage presentation, i.p. spread, and poor prognosis. It is histologically similar to serous papillary carcinoma of the ovary. Preclinical studies have shown that adenovirus-mediated expression of p53 in ovarian cancer cell lines causes growth inhibition and apoptosis in vitro and in vivo. Such studies provide the rationale for Phase I Adp53 gene therapy clinical trials in ovarian cancer. In the present study, we compared the efficacy of adenoviral vectors containing p53 (Adp53) or p21 (Adp21) in a papillary serous endometrial tumor cell line (SPEC-2) that contains mutated p53. Growth assays revealed that both Adp53 and Adp21 were efficacious in decreasing cell proliferation as assessed by anchorage-dependent and anchorage-independent growth assays. However, as compared with Adp53, the effects of Adp21 tended to be more transient and less marked. Strikingly, Adp21, but not Adp53, induced a G1 arrest in SPEC-2 endometrial adenocarcinoma cells. In contrast, as assessed by induction of hypodiploid peaks, free DNA ends detected by a terminal deoxynucleotidyl transferase-based assay, and annexin V positivity, p53 was more effective than p21 in inducing cell death by apoptosis. Compatible with the more efficient induction of apoptosis, Adp53, but not Adp21, induced a marked increase in expression of the preapoptotic molecule BAX without a concomitant change in expression of the antiapoptotic mediator Bcl-2. The differential effects of Adp53 and Adp21 on cell cycle progression and apoptosis may be related to the reversibility of p21-induced cell cycle arrest and the irreversibility of p53-induced apoptosis. Thus, at least in the papillary serous endometrial carcinoma cell line SPEC-2, Adp53 may be more effective than Adp21 as a gene therapeutic. Nevertheless, these preclinical studies suggest that papillary serous endometrial carcinoma is a potential target for p53- or p21-mediated gene therapy.
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PMID:Adenovirus-mediated expression of p53 or p21 in a papillary serous endometrial carcinoma cell line (SPEC-2) results in both growth inhibition and apoptotic cell death: potential application of gene therapy to endometrial cancer. 1065 59

The two anti-apoptotic proteins Bcl-2 and Bcl-x(L), and the two pro-apoptotic proteins Bax and Bcl-x(S) were measured by Western blotting in 51 neoplastic and 8 normal endometrial samples. The corresponding mRNA levels were analyzed by semiquantitative reverse transcriptase-polymerase chain reaction in a subgroup of 19 endometrial carcinomas. Neoplastic tissues had higher amounts of Bcl-2 protein than normal tissues (p < 0.051). Bcl-x(L) followed the same trend since its levels were higher in tumor than in normal samples (p < 0.048). Interestingly, Bcl-2 and Bcl-x(L) protein content showed a trend towards an inverse correlation (r = 0.27, p < 0.052). mRNA and protein levels directly correlated only with Bcl-2 (r = 0.63, p < 0.0032). Despite the fact that the amounts of Bcl-2, Bax and Bcl-x(L) proteins in the neoplastic population were not significantly differently distributed according to the clinicopathological features of the patients, the differences observed between normal and neoplastic samples suggest that these proteins may play a role in endometrial carcinoma: long-term follow-up studies will be required to confirm this hypothesis.
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PMID:Bcl-2, Bax, Bcl-x(L) and Bcl-x(S) expression in neoplastic and normal endometrium. 1070 44

Tamoxifen increases endometrial cell proliferation and the incidence of endometrial cancer in postmenopausal women. The purpose of this study was to evaluate apoptosis and apoptosis-related factors in endometrium in relation to tamoxifen exposure. We analyzed benign postmenopausal endometrium from breast cancer patients receiving tamoxifen (n = 35) and from controls (n = 24), and endometrial cancer tissue from tamoxifen-treated breast cancer patients (n = 15) and endometrial cancer from women without tamoxifen exposure (n = 51). Apoptosis was examined morphologically, and the percentage of apoptotic epithelial cells was defined as the apoptotic index. In the benign samples, the presence of apoptotic cells was also evaluated immunohistochemically by the expression of caspase-3 and the monoclonal antibody M30. The expression of Fas, FasL, and Bcl-2 was analyzed in all tissue samples. No differences were observed in the mean apoptotic index in benign endometrium in tamoxifen users (0.17%) versus controls (0.08%), or in tamoxifen-exposed (2.46%) versus nonexposed endometrial cancer (2.28%). However, the ratio of the apoptotic index with the previously reported proliferation index was lower in benign endometrium from tamoxifen users than in controls (0.02 +/- 0.026 vs. 0.05 +/- 0.03, Mann-Whitney U <0.005). In benign endometrium FasL was more frequently expressed in tamoxifen-users than in controls (chi(2) <0.05). We conclude that the apoptosis/proliferation ratio in benign endometrium from tamoxifen users is lower than in controls, indicating that the tamoxifen-induced higher proliferation is not compensated for by increased apoptosis. An imbalance between cell proliferation and apoptosis, and possibly suppression of the antitumor immune response by FasL overexpression in tamoxifen-exposed endometrium might play a role in the development of endometrial cancer in tamoxifen users.
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PMID:Apoptosis and apoptosis-associated parameters in relation to tamoxifen exposure in postmenopausal endometrium. 1273 25

A role for activins in regulating cellular transformation is suggested by the alpha-inhibin knockout mouse in which development of gonadal tumors is associated with elevated activin levels. It was the purpose of the current study to determine whether activin had similar actions on endometrial cell lines, specifically on a well differentiated estrogen-responsive endometrial adenocarcinoma cell line (ISH) and estrogen-unresponsive cells (HEC-50) obtained from a poorly differentiated endometrial adenocarcinoma. Activin was secreted by both adenocarcinoma cell lines. Using reverse transcription-PCR, messenger RNA type I and type II activin receptor subtypes were detected in both cell lines: expression of IB and IIB was approximately three- to fourfold greater in ISH cells than in HEC-50 cells, while activin receptor IA and IIA messenger RNA levels were approximately equal in both cell lines. Activin treatment (30-300 ng/ml) caused a dose- and time-dependent inhibition of ISH cells proliferation and resulted in a significant decrease in Bcl-2 protein and mRNA levels. No difference was observed in Bax expression. There was no significant effect of activin when the cultures of ISH cells were exposed to 17beta-estradiol. In contrast, activin showed a weak, but significant, mitogenic effect on HEC-50 cells without modifications in Bax and Bcl-2 mRNA and protein levels. The results demonstrate that activin is a regulator of endometrial cancer cell growth. 17beta-Estradiol may promote resistance of estrogen-responsive endometrial cancer cells to the growth-retarding effects of activin and one of the mechanisms might be a down-regulation of the activin receptors.
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PMID:Regulation of endometrial adenocarcinoma cell proliferation by Activin-A and its modulation by 17beta-estradiol. 1208 79

Considering the particular importance of angiogenesis and tumor suppressor genes expression in solid tumors, angiogenesis and Bcl-2 protein expression were evaluated in order to specify their role in the biology of endometrial carcinoma. Clinical material comprised 66 patients (postmenopausal, aged 52 to 76 years) with endometrial adenocarcinoma. For evaluation of angiogenesis immunohistochemical method was applied using DAKO EPOS Anti-Human Von Willebrand Factor/HRP antibodies. Morphometric method was applied to count angiogenic points (microvessels + single endothelial cells), using a light microscope with morphometric appliance. Angiogenic points density (APD) was defined as the density of AP per square mm. Immunohistochemical staining for Bcl-2 cytosomic protein expression was performed using MoAb124 (dilution 1:80, Dako A/S, Denmark) monoclonal antibodies. The percentage of 10% positive cells was considered as Bcl-2 positive tissue expression. Positive cytoplasmic reaction of Bcl-2 in 51.3% of patients with Stage I endometrial cancer, and in 23.8% and 0% of patients with II and III FIGO stage, respectively, was observed. No relationship between Bcl-2 tissue cytoplasmatic expression and tumor grade was found. However, an inverse correlation between cytoplasmatic expression of Bcl-2 and FIGO stage was observed. The APD (angiogenic points density) was increasing with the clinical (FIGO) stage of endometrial cancer, but it was not observed in the case of tumor histologic grade. Bcl-2 expression and angiogenesis may be a useful parameter in evaluation of the biology of endometrial adenocarcinoma as the study conducted showed the influence of Bcl-2 protein expression upon angiogenesis.
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PMID:Angiogenesis and Bcl-2 protein expression in patients with endometrial carcinoma. 1209 99

To make an initial inquiry into the correlation of development and prognosis with the expression of Bcl-2 protein in endometrial carcinoma, we detected the Bcl-2 protein expression in 40 normal and 60 malignant samples of the endometrium by means of an immunohistochemical technique. We observed that Bcl-2 expression varied with menstrual cycle, becoming stronger in proliferative phase and then declining in secretory phase. Bcl-2 expression in endometrial carcinoma was much weaker than that in normal endometrium, and Bcl-2 was particularly expressed in adenoacanthoma, papillary adenocarcinoma and simple adenocarcinoma. The higher grade and stage were, the stronger Bcl-2 expression was (P < 0.01). In 5 cases of endometrial carcinoma with hyperplastic endometrium, Bcl-2 expression of carcinoma was obviously weaker than that of hyperplastic endometrium. So we conclude that Bcl-2 overexpression may contribute to the formation of hyperplastic endometrium, that obvious reduction of Bcl-2 expression in endometrial carcinoma may promote apoptosis of cells, and that Bcl-2 over-expression may be associated with good prognosis.
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PMID:[A study of Bcl-2 expression in normal endometrium and endometrial carcinoma]. 1220 37

Apoptosis and proliferation were studied in 29 endometrial adenocarcinomas of the endometrioid type and characterized by the immunohisto-chemical pattern of estrogen receptor (ER) alpha and progesterone receptor (PR) expression. Intratumoral heterogeneous distribution of both ER and PR as well as of the proliferation marker Ki-67 was studied and quantified. Both density and heterogeneity of the two steroid receptors and Ki-67 varied, depending on the histological malignancy grade (grades 1-3, or G1-3); interestingly, however, the apoptotic index (Ai) was in the same range for all grades. Receptor staining was evaluated by three different methods: i) counting the percentage of stained cells (staining index), according to stereological principles; ii) the mixed method, a combination of the staining index results and ranking staining intensity; and iii) a superficial and rapid visual scoring. The three methods gave equal results. Apoptotic cells and bodies were generally scattered in the endometrial carcinoma but more frequently observed adjacent to necrotic foci. Bcl-2, known as anti-apoptotic factor, showed no correlation to apoptotic index, Ki-67 expression, ER, or PR. Overexpression of p53 was seen in two tumors of grade 3. In a detailed study of intra-tumoral microfoci performed on consecutively taken tissue sections, a higher staining index of both ER and PR was found in the areas of maximal proliferation compared with the areas of minimal proliferation in tumors of grades 1-2, but not in G3 tumors. Other covariations were also found when non-specified areas were studied. The Ki-67 index was both higher and more heterogeneous in G2-3 tumors than in G1 tumors. Our results indicate that there is an increasing discrepancy between cell death and cell proliferation with progressing tumor grade, which may contribute to the differences in tumor aggressivity.
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PMID:Apoptosis, proliferation, and hormone receptors in endometrial carcinoma: results depending on methods of analysis. 1246 93


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