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 bcl-2 proto-oncogene, which inhibits programmed cell death (apoptosis), has recently been found to be cyclically expressed in human endometrium. In order to investigate its role in endometrial hyperplasia and neoplasia, bcl-2 expression was studied in 25 cases of endometrial carcinoma and 20 cases of endometrial hyperplasia (eight simple, two complex, and ten atypical hyperplasias). Uniform intense cytoplasmic bcl-2 expression was found in all cases of non-atypical hyperplasia, and less strong positivity in eight out of ten cases of atypical hyperplasia. In well-differentiated carcinomas, nine out of ten showed weak to moderate bcl-2 expression, whereas six out of seven poorly differentiated carcinomas were bcl-2-negative. Moderately differentiated tumours were an intermediate group, with six out of eight being positive. Widespread localization of bcl-2 protein to the chromosomes of dividing cells was also demonstrated, regardless of cytoplasmic bcl-2 expression, with rare staining of interphase nuclei. Our findings suggest a role for bcl-2 in the natural history of endometrial neoplasia and studies are needed to determine its usefulness as a prognostic marker. The finding of bcl-2 localization to chromosomes has important implications for its mode and site of action.
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PMID:Nuclear and cytoplasmic bcl-2 expression in endometrial hyperplasia and adenocarcinoma. 855 85

Forty-two cases, including 21 uterine papillary serous carcinomas (UPSC) and 21 age-, nuclear-grade-, and clinical-stage-matched uterine endometrioid carcinomas (UEC), were studied immunohistochemically for p53 and bcl-2 in archival paraffin-embedded tissue. Compared to UEC (28.6% positive), UPSC (71.4% positive) had a significantly higher frequency of p53 overexpression (P = 0.005); furthermore, in a clinical-stage-matched fashion, a higher frequency of p53 overexpression was found in early-stage cases (P = 0.032), but not in late-stage cases. In a nuclear-grade-matched comparison, no statistical difference in p53 overexpression was identified between the two subtypes, although UPSC had stronger p53 immunoreactivity than UEC. Of UPSC, no difference in p53 overexpression was detected between tumors of early and late stages; additionally, in 5 cases, there was an abrupt transition from nonstaining morphologically benign glands to uniformly positive p53 nuclear staining in regions of intraepithelial carcinoma. Conversely, in UEC, there was a significant difference in p53 immunostaining between tumors of early and late stages (P = 0.01); no case had an abrupt transition for p53 immunostaining. For bcl-2 immunostaining, UEC had a significantly higher immunohistochemical staining score than did UPSC (P = 0.0002). In general, the staining intensity of bcl-2 diminished progressively from proliferative phase and hyperplastic endometrium to UEC and then to UPSC, with 3 of 21 (14.3%) UPSC being negative. These results suggest that p53 alteration may be an early event in the development of UPSC and may be related to its clinical aggressiveness, while it is a late event in UEC. Early detection of p53 nuclear accumulation may help to identify precursor lesions of UPSC. bcl-2 persistence is frequently associated with endometrial carcinoma, and failure to inactivate bcl-2 expression probably is related to the development of endometrial carcinoma.
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PMID:p53 overexpression and bcl-2 persistence in endometrial carcinoma: comparison of papillary serous and endometrioid subtypes. 862 27

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

The bcl-2 protein, which protects cells from apoptosis, is normally expressed in a number of adult tissues. Dysregulated bcl-2 expression, secondary to (14;18) chromosomal translocation, seems to promote the development of follicular lymphomas, and recent findings of bcl-2 protein in several solid tumors suggest that it might contribute to the genesis of many other neoplasms. bcl-2 is also highly expressed in normal proliferative endometrium and markedly down-regulated in secretory endometrium, which suggests that its expression is estrogen regulated. Because the development of most endometrial carcinomas is associated with hyperestrogenic states, we began the investigation of the role of bcl-2 in endometrial carcinogenesis by immunohistochemically quantifying its expression in proliferative, hyperplastic, atypically hyperplastic, and carcinomatous endometrium. The results of this study show that bcl-2 is relatively highly expressed in proliferative (n = 11) and hyperplastic (n = 18) endometrium, with respective mean staining scores of 3.59 and 3.47 (scale, 0-4), but is significantly (P < 0.001) down-regulated in atypical hyperplasia (n = 11; score, 0.82), and adenocarcinoma (n = 34; score, 0.86). bcl-2 expression did not correlate with stage, grade, estrogen-receptor, or progesterone-receptor expression. Polymerase chain reaction analyses of DNA isolated from several endometrial carcinomas were negative for (14;18) translocation involving the bcl-2 gene. Thus, bcl-2 apparently plays no role in the progression of atypical hyperplasia to carcinoma or in the development of high-grade or advanced-stage endometrial carcinoma. These results, however, do not rule out the involvement of bcl-2 in very early, preatypical hyperplasia phases of endometrial carcinogenesis. Finally, the marked difference in bcl-2 expression in hyperplastic and atypically hyperplastic glands might prove to be diagnostically useful in the often difficult distinction of these entities.
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PMID:bcl-2 is down-regulated in atypical endometrial hyperplasia and adenocarcinoma. 872 85

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

The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death. bcl-2 overexpression was originally described in follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. In this study we used immunohistochemistry to examine bcl-2 protein expression in endometrial hyperplasia and carcinoma. bcl-2 protein was observed in 4/4 cases of complex hyperplasia, 1/4 cases of complex atypical hyperplasia, and 10/29 cases of carcinoma. The staining observed in the cases of complex atypical hyperplasia and carcinoma was focal and less intense than the reactivity of normal proliferative endometrium. We conclude that bcl-2 protein is seldom overexpressed in complex atypical hyperplasia or carcinoma of the endometrium. Rather, in many cases of endometrial carcinoma bcl-2 expression appears to be decreased.
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PMID:bcl-2 expression in endometrial hyperplasia and carcinoma. 894 65

Apoptosis is a process of single-cell deletion requiring active participation of the cell in its own demise. First described in 1972, it is now known to play a major role in embryogenesis, tissue homeostasis and neoplasia. Apoptosis can be initiated when DNA damage occurs causing the cell to pause in its reproductive cycle. If the DNA damage is beyond repair, the cell proceeds to apoptotic cell death. When the genetic mechanism(s) involved in the pathway of apoptosis is altered, the cell does not die. Further mutations occur by proliferation and such multiple mutational events can lead to a malignant phenotype and cancer growth. The tumour suppressor gene p53 causes a DNA-damaged cell to rest and attempt repair. If damage is irreparable, p53 levels will continue to increase, initiating apoptosis. Mutation of p53, found in approximately 50% of cancers, can stop the apoptotic process. Increased bcl-2 expression, an apoptosis inhibitor, also plays a role in cellular transformation and cancer growth. Its altered expression occurs in the presence of oncogene expression. This paper reviews the role of apoptosis in malignant transformation, cancer growth, and response to therapy for gynaecological cancers. For cervical cancer and its precursors, data on apoptotic index, bcl-2 and Bax expression are presented and discussed in relationship to human papillomavirus expression. In ovarian epithelial malignancies, the role that apoptosis plays in chemotherapeutic responses is reviewed. The data for endometrial cancer are currently limited to apoptotic index.
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PMID:The role of apoptosis in gynaecological malignancies. 918 26

bcl-2 protein is expressed in normal endometrium and seems to be under hormonal control. Its role in endometrial carcinoma (EC) is largely unknown. EC can serve as a good model to investigate the role of bcl-2 in hormone-dependent neoplasia, because EC shows a spectrum of hormonally induced changes in which bcl-2 might have a potential role. p53, a tumor suppressor gene, is the most commonly mutated gene in human cancer and is a frequent abnormality in advanced EC. There is interaction between p53 and bcl-2 proteins in the regulation of physiological programmed cell death and in malignant processes. In this study, we performed immunohistochemical investigations of the expression of bcl-2 and p53 in 57 ECs, along with estrogen and progesterone receptors (ERs, PRs), to correlate the expression patterns of bcl-2 and p53 in different grades of EC with relation to clinicopathologic parameters. The average age of the patients was 61 years. Among 57 ECs, there were 13 noninvasive ECs and 44 ECs with various depths of invasion. p53 was positive in 21 of 57 cases, and bcl-2 was positive in 42 of 57. ER and PR were positive in 24 of 57 cases; PR and ER alone were positive in 15 and 2 cases, respectively. bcl-2 expression is present in ECs, and its expression is related to grade and stage. bcl-2 expression is strongly associated with PR, whereas p53 is associated with higher grade and is inversely related to PR positivity.
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PMID:bcl-2 and p53 in endometrial adenocarcinoma. 923 85

Endometrial carcinoma is the commonest malignancy of the female genital tract. The pathogenesis is complex and at least three pathogenetic subtypes exist with different prognostic implications. The molecular events involved remain poorly defined but several genes are involved and mutations of tp53, WAF1/CIP1, PTEN, bcl-2 and c-erbB-2 have been implicated. Although care is needed in interpreting the results, the majority of these mutations can be detected immunohistochemically and therefore have the potential to aid the pathologist and surgeon in assessing the prognosis of a tumour. However, for the time being, no molecular marker is as valuable in determining prognosis as conventional parameters such as tumour type, grade and vascular space involvement.
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PMID:Recent advances in the histopathology and molecular pathology of carcinoma of the endometrium. 982 17

The role of p53 and bcl-2 apoptosis related proteins in the pathogenesis of endometrial cancer remains unclear. We immunohistochemically examined 133 surgically removed tumour specimens from patients with stage I endometrial cancer for p53 oncoprotein nuclear expression and bcl-2 cytoplasmic reactivity. 114/133 (86%) cases were of the endometrioid histological sub-type. A cut-off point of 10% of cells with strong reactivity was used for positivity. Positive p53 expression was observed in 12/133 (9%) and positive bcl-2 in 40/133 (30%) cases. p53 expression was not related to bcl-2 expression. No association of p53 and bcl-2 with depth of myometrial invasion, vascular invasion or histological grade was observed. However, continuous variable analysis revealed a trend of low grade cases to have a higher percentage of bcl-2 positive cells (16.3 + 27% vs. 7.8 + 16%; p = 0.09, unpaired two tailed t-test). Interestingly, a statistically significant association of p53 positivity with age was also observed (p = 0.03). A strong association of high grade with depth of myometrial invasion (p = 0.006) and vascular invasion (p = 0.0001) was also noticed. In addition, the presence of adenomyosis was also associated with low grade (p = 0.01) and absence of vascular invasion (p = 0.02). We conclude that although loss of bcl-2 protein expression and p53 mutant protein nuclear accumulation are early events in the endometrial cancer progression, histological grade and vascular invasion remain the most important factors defining local invasive behaviour of endometrial cancer.
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PMID:Bcl-2 and p53 expression in stage I endometrial carcinoma. 985 78


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