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

The expression of mutated p53 protein was studied in paraffin-embedded, formalin-fixed tumour specimens from 183 women with endometrial carcinoma. Fifty-five per cent of the specimens were negative, whereas the staining intensity was weak, moderate or strong in 15, 2 and 28% of cases, respectively. Strong p53 expression (> 75% of the cells stained) was more common in uterine papillary serous cancers and clear cell cancers than in other tumour subtypes (P < 0.001), as well as in poorly differentiated tumours (P < 0.01) and in tumours with nuclear grade 3 (P < 0.0001). Strong p53 expression was also more frequently found in aneuploid tumours (P < 0.0001) and in tumours with a high S-phase fraction (P < 0.001). Strong p53 expression was highly predictive of poor survival in the univariate analysis (P = 0.006) and in the Cox multivariate analysis which included age, stage and grade. However, it lost most of its impact when the strongly prognostic nuclear grade and ploidy were added to the multivariate models.
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PMID:Mutant p53 protein as a predictor of survival in endometrial carcinoma. 869 59

The bcl-2 gene product inhibits programmed cell death (apoptosis). The expression of this protein has been examined in normal endometrium and found to be cycle dependent with consistent expression in the proliferative phase. In the current report, bcl-2 gene expression was examined in 88 endometrial biopsies that showed 99 histologic patterns ranging from proliferative endometrium to carcinoma. Whereas expression was always detected in 17 samples of proliferative endometrium, eight cases of simple hyperplasia, and five cases of complex hyperplasia, expression was detected in only five (42%) of 12 atypical hyperplasias and in only 27 (47%) of 57 carcinomas. In atypical hyperplasia and carcinoma showing expression, both staining intensity and distribution were less than that seen in their benign counterparts. Three of five biopsies showing both benign endometrium and carcinoma showed positivity in benign but not in malignant glands. In endometrial carcinoma, bcl-2 expression did not correlate with grade, stage, or survival. In addition, in cases of carcinoma, a negative correlation between bcl-2 and p53 expression, which has been reported in other tumors, was not observed in this study. The invariable expression of bcl-2 in proliferative endometrium suggests that this protein may be important for cell survival. Its role in preventing cell death, however, appears to be frequently bypassed in atypical hyperplasia and endometrial carcinoma possibly by other factors impeding programmed cell death. Thus, if an apoptotic pathway usually blocked by bcl-2 expression would not necessarily lead to cell death. Defects in an apoptotic pathway such as the transforming growth factor-beta pathway, which can be blocked by bcl-2, may possibly account for the phenomenon observed in this study.
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PMID:bcl-2 expression and the development of endometrial carcinoma. 872 80

Endometrial cancers may be divided into two groups, reflecting differences in clinical behavior and pathogenesis. Endometrioid adenocarcinoma, which accounts for the majority of endometrial cancers, typifies the group of endometrial carcinomas that develop from atypical endometrial hyperplasia in the setting of excess estrogenic stimulation. In contrast, serous carcinomas are representative of endometrial tumors that occur in older women who have endometrial atrophy and lack the typical endometrial cancer risk factors reflecting unopposed estrogen exposure. Serous carcinomas are frequently associated with p53 abnormalities and appear to develop from a surface lesion termed endometrial intraepithelial carcinoma. Although serous carcinomas are rare, these highly aggressive tumors account for a disproportionate number of endometrial cancer deaths. Further delineation of the estrogen-dependent and estrogen-independent pathways of endometrial carcinogenesis may be useful in developing comprehensive chemopreventive approaches for endometrial cancer.
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PMID:Endometrial cancer chemoprevention: implications of diverse pathways of carcinogenesis. 874 91

A number of oncogenes and tumor suppressor genes that may serves as surrogate biomarkers of transformation are altered during the process of endometrial carcinogenesis. Overexpression of HER-2/neu occurs in 10% of endometrial adenocarcinomas and correlates with intraperitoneal spread of disease and poor survival. The c-myc oncogene is amplified in 10% of cases. Point mutations in codon 12 of the K-ras oncogene have been reported to occur in 10-20% of endometrial cancers. K-ras mutations also have been noted in some endometrial hyperplasias, which may represent an early event in the development of some endometrial cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 20% of endometrial adenocarcinomas. Overexpression of p53 is associated with advanced stage and poor survival. Because p53 mutations have not been observed in endometrial hyperplasias, this is thought to be a relatively late event in endometrial carcinogenesis. Microsatellite instability has also been noted in approximately 15% of sporadic endometrial cancers, but mutations in DNA repair genes have not yet been reported. Chemoprevention trials in endometrial cancer may be feasible due to the existence of a premalignant lesion and surrogate biomarkers.
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PMID:Biomarkers in the endometrium. 874 93

The degree of expression of p53 and proliferating cell nuclear antigen (PCNA) was measured in archival samples from 221 patients managed surgically for endometrial carcinoma between 1979 and 1983. With use of primary antibodies to the p53 protein (DO7) and PCNA (PC10), immunoperoxidase nuclear staining of paraffin-embedded tissue was performed. The computerized CAS200 Image Analysis System was used to determine the percentage of nuclear area stained. There was no evidence to conclude that progression-free survival differed with respect to PCNA expression. In contrast, intense p53 expression (66% or more nuclear area stained) was significantly associated with compromised progression-free survival both in the analysis of all stages (P < 0.001) and in the subset of patients with stage I disease (P < 0.001). Intense expression of p53 was significantly associated with other prognostic indicators, including stage, grade, depth of myometrial invasion, histologic subtype, cytologic findings, DNA ploidy, and HER-2/neu expression. Multivariate analysis identified four independent prognostic factors for progression-free survival in endometrial carcinoma: intense p53 expression, histologic subtype, DNA ploidy status, and HER-2/neu expression. When none of these four independent factors are present, the 4-year progression-free survival is 96%. In contrast, it is 63% when one or more of these factors are present (P < 0.001) and 40% when two or more factors are present (P < 0.001).
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PMID:Prognostic value of p53 and proliferating cell nuclear antigen expression in endometrial carcinoma. 875 48

Overexpression of p53 protein has been reported to correlate with a poor prognosis in endometrial cancer. Most endometrial adenocarcinomas are clinical stage I at the time of diagnosis and the majority of women to die of this neoplasm had stage I disease at initial presentation. The aim of our study was to evaluate the prognostic significance of p53 overexpression in early stage endometrial carcinoma. Ninety-two patients with surgically treated endometrial adenocarcinoma FIGO stage I were examined for overexpression of immunohistochemically detected mutant p53 protein. Follow-up time ranged from 0.4 to 137.8 months (mean, 34.8). Thirteen women died of their tumor. A nuclear staining reaction for p53 was observed in eight cases. Women with p53 protein overexpression showed a significant poorer overall survival in univariate analysis (relative risk, 4.78; 95% confidence interval, 1.56-14.61; P = 0.006, Wald test) and also in multiple analysis adjusted for grading (relative risk, 4.39; 95% confidence interval, 1.39-13.90; P = 0.01, Wald test). Histological grading and histologic stage did not correlate with p53 protein overexpression (P = 0.26, P = 1.0, respectively, exact chi 2 test). Immunohistochemically detected p53 protein overexpression in early stage endometrial adenocarcinoma could aid in predicting prognosis and subsequently have some impact on adjuvant therapy.
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PMID:p53 protein overexpression in early stage endometrial cancer. 875 52

Histopathologic changes ranging from simple cystic hyperplasia to carcinoma in situ may be observed in adenomyotic foci in patients with endometrial carcinoma. These changes can be an area of concern and physicians should be aware of their clinicopathologic significance. We studied a total of 94 patients, including endometrial carcinoma with (28 patients) and without adenomyosis (56 patients), and control group of adenomyosis cases (10 patients) without endometrial carcinoma. The histopathological changes in adenomyosis in patients with endometrial carcinoma varied from endometrial glands resembling the basal endometrium (13 of 28) through simple hyperplasia (8 of 28) to complex atypical hyperplasia, resembling carcinoma in situ (7 of 28). Formalinfixed paraffin-embedded tissues from 55 patients (45 endometrial carcinomas and 10 control adenomyosis) were stained with monoclonal antibodies against P53. P53 positivity was not detected in adenomyosis cases without endometrial carcinoma but was present in 7 of the endometrial carcinoma-related cases. P53 positivity was found in 14 of 45 endometrial carcinomas studied. In all of the adenomyosis-positive cases, the endometrium was also positive. In conclusion, adenomyosis with a range of hyperplastic to atypical changes is not uncommon in adenocarcinoma patients. Our findings regarding P53 positivity in adenomyosis are consistent with the hypothesis that hyperplastic and atypical changes in adenomyosis might be due to a carcinogenic field effect in the vicinity of endometrial carcinoma rather than by direct invasion.
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PMID:P53 expression in adenomyosis in endometrial carcinoma patients. 875 56

The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of these changes. Of 122 endometrial carcinomas, 33 (27%) showed overexpression of p53 in the nucleus and 66 (54%) in the cytoplasm. Mutation in the p53 gene was found in 16 (13%) cases but showed no significant association with patient survival. Nuclear p53 overexpression was associated with poor survival (48% vs 80% alive in negative tumours 5 years post operatively, P < 0.001). In contrast, cytoplasmic p53 overexpression was associated with better survival (85% vs 55%, P < 0.001). When patients were separated into prognostic subgroups according to established clinical markers, these associations remained significant within most subgroups examined. In multivariate analysis adjusted for surgical stage, histological grade and type and vascular invasion, both nuclear p53 overexpression [hazard ratio 4.9 (95% CI 1.3-17.6). P = 0.016] and cytoplasmic overexpression [0.25 (0.06-0.98), P = 0.047] were independent prognostic factors. Immunohistochemical assessment of p53 overexpression in the nucleus and cytoplasm could provide useful prognostic information for the management of patients with endometrial cancer.
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PMID:Overexpression of p53 protein is an independent prognostic indicator in human endometrial carcinoma. 876 70

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.
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PMID:Immunohistochemical analysis of endometrial adenocarcinoma for bcl-2 and p53 in relation to expression of sex steroid receptor and proliferative activity. 881 80

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


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