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

It is widely recognized that endometrial carcinoma represents one of the most frequent types of pelvic malignancy in women. Recent improved knowledge about population at risk, the criteria of classification of endometrial hyperplasia, different potential for neoplastic transformation for each type of neoplasia, and asymptomatic latency of the pathology allow some considerations. Endometrial cytology is of basic importance in a mass screening programme due to its low cost, accuracy and feasibility. The combination of hysteroscopy and endometrial biopsy is the diagnostic method of choice for symptomatic patients. It permits the elimination of curettage in the diagnostic management in over 95% of cases, with obvious advantages, better diagnostic accuracy and greater convenience for patients and doctors.
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PMID:Early detection of endometrial cancer and hyperplasia: a reappraisal. 205 51

The hormone sensitivity of endometrial carcinoma is related to the presence of steroid hormone receptors. The determination of progesterone receptors has been proposed in order to predict clinical prognosis and to aid treatment selection. The integrity of the hormone receptor system and postreceptoral events in tumors is essential to endocrine therapy response. Nevertheless, although hormone receptors are present in a large number of endometrial carcinomas, only 30% of cases respond to hormone therapy. In some neoplasms the receptors can be present, but not functioning, or else neoplastic transformation could have induced alterations in processes after hormone-receptor interaction.
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PMID:Hormone receptors and enzymatic activities in human endometrial adenocarcinoma. 214 74

In a series of 52 biopsy specimens (31 endometrial carcinomas, 10 atypical endometrial hyperplasias, and 11 cases of normal endometrium), DNA ploidy and S-phase cell fraction were estimated in paraffin-embedded material. DNA aneuploidy was detected in 2 of the 10 atypical endometrial hyperplasias and 7 of the 31 endometrial carcinomas. The majority of aneuploidy was found to be connected with the loss of tumor differentiation. No ploidy disturbances were found in normal endometrium. The S-phase cell fraction value of normal endometrium was significantly lower when compared with that of endometrial carcinoma. The broad variation in S-phase cell fraction values of the endometrial carcinomas and atypical endometrial hyperplasias was in contrast with the low variability of S-phase cell values of normal endometrium. Very low incidence of aneuploidy in the group of well differentiated endometrial carcinomas (Grade I) enables the suggestion that the presence of aneuploidy predicts a more aggressive disease and that the detection of an aneuploid stemline in atypical endometrial hyperplasia may already indicate the neoplastic transformation.
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PMID:Flow cytometry (FCM) analysis of endometrial hyperplasia and carcinoma. 223 10

On the basis of experimental research, using rabbit uterine epithelium as a model, it is postulated that human endometrial hyperplasia or carcinoma may be due to derangement of intrinsic growth mechanisms such as cell proliferation, migration, loss and differentiation. Ovarian hormones, estrogen inhibitor or amplifying factors, prostaglandins, stroma-epithelial interactions, proteolytic activity and hormone receptors, all regulate the described intrinsic growth mechanisms, and their excess or lack could result in altered growth patterns. It is also proposed that different types of endometrial carcinoma could result from neoplastic transformation of cells at different stages of differentiation. Since cells at those stages could respond to various hormones in different ways, it would seem of therapeutic value to know the cell of origin in each type of endometrial carcinoma.
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PMID:A developmental view of endometrial hyperplasia and carcinoma based on experimental research. 714 71

We studied the abnormal expression of a glycoconjugate that appears in the process of neoplasia of endometrial cells and tried to shed light on the mechanism of their expression. Furthermore, we evaluated the effectiveness of its use in clinical application. 1. Investigation of abnormal expression of glycoconjugate We performed an immunohistochemical study on the expression of blood group-related carbohydrate antigens in endometrial cells, and found that carbohydrate side chains with galactose and fucose at their terminals were increased in association with neoplastic transformation. Using anti-endometrial cancer monoclonal antibody MSN-1, we showed that abnormal expression had already been induced in endometrial hyperplasia and increased as the lesions grew worse. A biochemical study of glycolipids showed that sulfatide (one of the sulfoglycolipids) was produced in endometrial cells, and that it varied in amount depending on the menstrual cycle, and was increased in endometrial cancer cells. Hydroxylation, which is recognized in cells in the fetal period, was seen in the ceramide region of these glycolipids. 2. Shedding light on the mechanism of the abnormal expression of glycoconjugate We examined normal and neoplastic endometrial cells for differences in the level of galactosyltransferase (GT) and fucosyltransferase (FT). Immunohistochemical staining with monoclonal antibody 8628 (an anti-GT antibody) gave the following results: GT gave a fine granular staining confined to the cytoplasma between the nucleus and glandular lumen in 70% of the cares of normal endometrium: In contrast, GT was found extensively in either a coarse granular state or spread diffusely throughout the cytoplasm in about 70% of the endometrial cancer specimens. We were also able to determine FT activity in normal and cancerous endometrial tissues by our newly developed method. The levels of alpha1-2FT, alpha 1-3FT and alpha 1-4FT were higher in endometrial cancer than in normal endometrium. Furthermore, we determined the activity of alpha 1-2FT and alpha 1-4FT in both endometrial cancer tissue and cell cultures derived from gynecological cancer, and examined the relationship between their activity levels and expression of the antigen recognized by MSN-1. There was a positive correlation between them. SNG-II cells were classified in terms of their reactivity to MSN-1 into two groups: 1) SNG-S, which was strongly reactive to MSN-1, and 2) SNG-W, which was weakly reactive to the antibody. FT activity was compared between these two cell groups. There was a marked difference in alpha 1-4FT activity between these two groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Abnormal expression of glycoconjugate associated with the development of endometrial cancer: a basic study and its usefulness in clinical application]. 837 Oct 8

For several decades, clinical and histologic assessment of various phenotypic properties has provided a basis for treatment planning. However, it is recognized that, preoperatively, clinical assessment identifies only 20% of patients with advanced disease. Furthermore, the variability in intraoperative sampling, the subjectivity and limitations of histologic interpretation, and the variability in response to standardized treatment modalities represent concerns associated with the current treatment of endometrial carcinoma. Presumably, early dissemination, early recurrence, treatment refractoriness and, ultimately, compromised survival are reflections of the inherent biologic characteristics of the tumor. A reasonable assumption is that proscribed molecular events determine various behavioral characteristics of tumors that become manifested at the time of transformation rather than evolving as the tumor volume increases. Therefore, the identification of one or more of these quantifiable molecular variables that directly or indirectly assess tumor biology would assist clinicians in determining patient risk status and in selecting treatment options. As noted, DNA ploidy is an independent, broadly applicable, quantifiable predictor of progression-free survival in patients with endometrial cancer and, therefore, warrants designation as a major prognostic factor or therapeutic determinant. Aneuploidy implies the presence of an abnormal quantity of genomic material and imparts a progressively less favorable prognosis as the DNA index increases. These assayable aberrancies of cellular DNA content presumably reflect the more extreme alterations at the molecular level. Because neoplastic transformation is generally a multistep process, aberrations in several proto-oncogenes or tumor suppressor genes (or both) presumably must be realized before a clinical malignancy develops. A number of genes that encode for various regulatory proteins are overexpressed in endometrial cancer. Whether these aberrancies are fundamental to the pathogenesis of this disease process is unclear. Nevertheless, there appears to be an association between DNA ploidy and the overexpression of several regulatory genes, such as c-fms, K-ras, HER-2/neu, and p53. Although overexpression of these oncogenes and tumor suppressor genes harbor prognostic significance in endometrial cancer, the ploidy status of the tumor appears to represent the most cogent objective variable. As the etiopathogenesis of endometrial carcinoma becomes more discernible, one can envision a limited number of tissue-specific molecular-genetic indices characterizing the risk status of patients. Because the estimated number of deaths from endometrial cancer has doubled since 1987, reassessing of the therapeutic determinants for this disease process is important. The management objective for endometrial cancer by the turn of the century should be the identification of patients at high risk for advanced disease or post-treatment recurrences (or both) at the time of clinical declaration of symptoms and diagnosis. Such pretreatment identification would afford patients at high risk for advanced or recurrent disease access to physicians with special expertise and would facilitate the evaluation and application of new or modified therapeutic modalities. Equally important would be the identification of patients at low risk for untoward outcome, thereby avoiding the cost and morbidity of excessive therapeutic measures.
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PMID:Endometrial neoplasia: prognostic significance of ploidy status. 886 93

We analysed p16 gene alteration and p16, cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D1, cyclin D2, cyclin D3 and retinoblastoma protein (pRb) expression in ten normal endometriums (PE), 18 endometrial hyperplasias (EH) and 35 endometrial cancers (EC). Two of ten PE (20%), nine of 18 EH (50.0%) and 29 of 35 EC (82.9%) exhibited p16 nuclear staining. p16 expression was significantly higher in EC than EH (P = 0.0119). In the six p16 (-) EC, one was considered to have reduced gene dosage consistent with possible homozygous deletion of the CDKN2 gene and three had methylation in 5'CpG island in the promoter region of the p16 gene, whereas none showed such reduced gene dosage and four had methylation in the nine p16 (-) EH. Strong CDK4 staining was observed in 12 of 35 EC (34.3%) and one of 18 EH (5.6%). The strong expression of CDK4 was higher in EC than in EH (P = 0.0399). The expression of CDK4 was higher in EH than PE (P = 0.0054). The abnormalities of p16-cyclin D/CDK-pRb pathway were detected in 18 of 35 EC (51.4%). In conclusion, the expression of p16 and CDK4 may be an early event in the neoplastic transformation of endometrial cancer.
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PMID:The role of p16-cyclin d/CDK-pRb pathway in the tumorigenesis of endometrioid-type endometrial carcinoma. 1068 82

Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of human endometrial adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone and thereby serve to modulate the tissue levels of bioactive E2. To elucidate the possible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36 endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2 using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17beta-HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal endometrium was present in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2 immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of 46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and carcinoma cases there were significant positive correlations between 17beta-HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cases, a significant inverse correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2 messenger RNA. No significant correlations were detected between 17beta-HSD type 2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade. These data indicated that the expression of 17beta-HSD type 2 in hyperplastic and/or neoplastic endometrium may represent altered cellular features through hyperplastic and neoplastic transformation. However, 17beta-HSD type 2 may also play some protective and/or suppressive roles toward unopposed estrogenic effects through inactivating E2 in situ, especially in premenopausal patients.
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PMID:The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma. 1144 21

Telomerase activation can be considered as a critical step in cell immortalization. The enzyme elongates or maintains telomere length by adding to its end tandem TTAGGG repeats by using its endogenous RNA template. Telomerase is not detectable in most somatic cells but is upregulated in germ line cells and in 85-90% of human cancers, which suggests important role of telomerase in neoplastic transformation. Consequently, telomerase has been proposed as a potentially highly selective target for the development of antiproliferative agents. Platinum complexes are widely administrated in cancer therapy. A conjugate of selenite with diammineplatinum [(NH(3))(2)Pt(SeO(3))(2)] is a novel potential anticancer drug. Using alkaline single cell gel electrophoresis (comet assay), we showed that the drug at 5-30 microM induced concentration-dependent damage to DNA of endometrial cancer cells derived from tumor samples. Sodium ascorbate at 10 and 50 microM reduced the extent of the DNA damage evoked by the drug. (NH(3))(2)Pt(SeO(3)) reduced telomerase activity in the cells in a concentration-dependent manner as measured by using the telomere repeat amplification protocol (TRAP) assay. This effect was independent of sodium ascorbate. Therefore, mutagenic effects of the conjugate can be reduced by well-recognized antimutagen, sodium ascorbate, but it can still retain ability to affect neoplastic transformation. The results obtained indicate that (NH(3))(2)Pt(SeO(3)) may specifically inhibit telomerase activity in endometrial cancer cells.
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PMID:Inhibition of telomerase activity in endometrial cancer cells by selenium-cisplatin conjugate despite suppression of its DNA-damaging activity by sodium ascorbate. 1175 89

Several recent advances have been made in our understanding of the pathogenesis of endometrial tumours, particularly endometrioid endometrial carcinoma (EEC). Mutations in the PTEN gene and microsatellite instability (MSI) are common genetic abnormalities in EECs, and distinguish these lesions from other histological subtypes of endometrial carcinoma. Endometrial precancers are monoclonal lesions that share a common genetic lineage with invasive EEC, including PTEN mutations and MSI. Mutations of the PTEN tumour suppressor gene have been identified in histologically normal-appearing endometrium exposed to oestrogen, 18-55% of endometrial precancers and 26-80% of EECs. PTEN has been shown to play several roles in tumour suppression, including cell cycle arrest and promotion of apoptosis. Loss of PTEN function predisposes endometrial cells to neoplastic transformation, particularly in high-oestrogenic states. MSI is another common alteration seen in EECs and endometrial precancers, and some studies have reported an association between MSI and PTEN mutations. The replication error that results in MSI may facilitate the development of PTEN mutations in some, but not all, cases of EEC. The prognostic significance of PTEN gene mutations and MSI in endometrial carcinoma is controversial. Further study is needed to delineate the different pathogenetic pathways of EEC and their natural history.
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PMID:PTEN mutations and evolving concepts in endometrial neoplasia. 1180 78


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