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

Several recently developed techniques have been applied to the study of endometrial lesions. These include the evaluation of K-ras abnormalities in patients with endometrial hyperplasia to identify those at high risk to develop carcinoma, the analysis of p53 abnormalities to distinguish between endometrial hyperplasia and carcinoma, the use of p53 for predicting clinical outcome in patients with endometrial carcinoma, and PCNA immunostaining of endometrial lesions with secretory activity. However, these studies should be regarded at this juncture as auxiliary, at best, to the cytological and histopathologic examination of human endometrial disorders.
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PMID:New concepts in the diagnosis and prognosis of endometrial carcinoma. 793 50

Using immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinicopathological parameters in patients with endometrial cancers. Formalin-fixed and paraffin-embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear-cell type, 1) were stained with anti-p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer. Lymph-node metastasis was also related to p53 overexpression with marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis showed p53 overexpression to be associated with a poor outcome in endometrial cancer patients. However, multivariate analysis using the stepwise Cox proportional-hazard model showed that whereas lymph-node metastasis, a personal history of cancer and muscular invasion were related to poor survival rates, p53 overexpression was not. Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively.
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PMID:Clinicopathological characteristics of p53 overexpression in endometrial cancers. 801 10

The tumour-suppressing gene p53 may undergo mutation by a variety of mechanisms, thus losing its tumour-suppressing activity, and ultimately behaving like an oncogene. The PAb 1801 monoclonal antibody is known to recognise both wild type and mutated p53, although in practice it seems to show a higher reactivity with the mutated gene product in several human tumours. We studied p53 overexpression in a series of 36 human tumours (17 mammary ductal infiltrating carcinomas, 11 endometrial carcinomas and 8 uterine cervical carcinomas) by means of immunohistochemistry using the PAb 1801 antibody and the streptavidin-biotin peroxidase technique. Furthermore, all tumours were screened for mutations in the "hot spot" regions of the p53 gene (exons 5 to 8) by means of SSCP (single strand conformation polymorphism) DNA analysis following amplification of the target exons using the polymerase chain reaction. A good correlation (75-100%) between positive immunohistochemistry and p53 mutations was observed in mammary and endometrial cancer, whereas mutations were detected in only two out of seven immunoreactive cervical carcinomas. Following these results, immunohistochemistry with the PAb monoclonal antibody may be safely used as a screening tool for the detection of mutated p53 in clinical samples of mammary and endometrial cancer, whereas it should be complemented with DNA analysis in cervix carcinoma.
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PMID:Identification of p53 mutations by means of single strand conformation polymorphism analysis in gynaecological tumours: comparison with the results of immunohistochemistry. 801 9

Abnormalities of p53, a tumor suppressor gene, have been considered to play an important role in tumorigenesis. Clinically, overexpression of p53 has been reported to correlate with poor prognosis in several types of tumors. In this study, we examined 221 cases of endometrioid endometrial carcinoma for overexpression of p53 using immunohistochemistry in patients with a median follow-up of 41 months. Immunohistochemical analysis was performed with monoclonal antibody pAb1801. Overexpression of p53 was detected in 47 of 221 cases (21.3%). There was a statistically significant correlation between p53 overexpression and poor prognosis (P < .0001). In the early stages of cancer (stages 1 and 2), p53 was overexpressed in 11 of 22 patients (50%) who died or had a recurrence during follow-up. In contrast, overexpression was detected in only 14.7% of the 156 disease-free patients during the same period (P < .0001). In advanced stages (stages 3 and 4), tumors from patients with recurrent disease had a higher frequency of overexpression (41.2%; 7 of 17) than those of disease-free patients (23.1% 6 of 26). However, the difference between these frequencies was not statistically significant. In multivariate analysis using the Cox proportional hazard model, p53 overexpression was an independent risk factor when compared with clinical stage, nuclear grade, and patient age. Our results indicate that p53 immunohistochemical evaluation of the most common form of endometrial cancer may be useful in identifying cases of aggressive carcinoma, especially in the early stages.
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PMID:Prognostic significance of p53 overexpression in endometrial cancer. 806 61

Endometrial cancers have been considered to be less prevalent in Japan than in Western countries. However, with the increase in life expectancy, the Westernization of the Japanese diet, and changes in the hormonal environment, the prevalence of the disease has gradually increased even in our country. Similar increases in cancers of the breasts, lungs, colons, and ovaries have been noted in recent years. Much is still unknown regarding the pathogenesis and natural history of endometrial cancer. Although endometrial hyperplasia is considered to be a precancerous lesion of endometrial carcinoma, the relationship between those diseases has not been elucidated to the same degree as that between cervical cancer and cervical dysplasia, or carcinoma in situ. Research findings in genetic oncology have revealed that tumorigenesis involves a multi-step process. It is probable that activation of multiple genes, inactivation of anti-oncogenes, and disappearance of normal inhibitor genes occur in the process of the development of endometrial cancer. The purpose of this study is to elucidate the relationship between oncogenes and the development of endometrial cancer. In addition, the significance of endometrial hyperplasia as a clinical entity is also be evaluated. The roles played by oncogenes in endometrial cancers and endometrial hyperplasias were examined using the most recent molecular biological and immunohistochemical methods. Also, the differences in cellular proliferation and tissue invasiveness were discussed. Results obtained were as follows. Evaluation of cell proliferation (PCNA, FCM) revealed that there was no difference in proliferative activity between atypical hyperplasia and well differentiated adenocarcinoma. Evaluation of oncogene abnormalities (c-myc,c-erbB-2,K-ras,p53) revealed that the development of endometrial cancer was a multistep process involving several oncogenes, as it has been noted in the development of other cancers. Evaluation of extracellular matrix and related factors (cathepsin D, laminin, type IV collagen, tenascin, CD44) showed that tissue invasiveness differed between atypical hyperplasia and well differentiated adenocarcinoma.
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PMID:[Evaluation of the degree of biological behavior in endometrial hyperplasia and endometrial carcinoma: an investigation of proliferative activity, oncogene, and extracellular matrix]. 810 84

Alterations of the retinoblastoma (Rb) gene were evaluated in nine primary endometrial adenocarcinomas that we had previously analyzed for the presence of Ki-ras activations and p53 alterations and in three endometrial carcinoma cell lines. Loss of mRNA expression in the Rb gene was detected in two of the 12 tumors. Internal deletions of Rb cDNA were observed in two tumors; one was a deletion of exon 21 in a primary carcinoma, and the other was a deletion of exon 8 in one allele in one cell line. Loss of heterozygosity of the Rb gene, which was detectable by polymorphisms in introns 1 and 17, was analyzed using polymerase chain reaction-restriction fragment length polymorphism analysis in 29 endometrial carcinomas. Of 13 heterozygous cases, two cases (15%) showed loss of heterozygosity. We therefore suggest that alteration of the Rb gene, as well as activation of the Ki-ras gene and alterations of the p53 gene, plays a significant role in the etiology of endometrial adenocarcinoma.
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PMID:Alterations of the Rb gene and its association with Ki-ras activation and p53 inactivation in endometrial adenocarcinoma. 810 95

The isolation of genes that predispose to familial disease is an important goal in cancer research. The identification of such genes "opens up" the possibility of genetic diagnosis in families so that individuals who are at risk of cancer through inheriting a predisposing mutation can be identified. Genes that are involved in familial cancer syndromes may also be important in the pathogenesis of sporadic forms of the disease, which are often more common. In the search for genes that predispose to familial breast and ovarian cancer much recent progress has been made. A locus on the long arm of chromosome 17, in the interval 17q12-21, has been identified by genetic linkage, and appears to be responsible for disease in approximately 40% of breast cancer families and most families that contain breast and ovarian cancer. The region containing this locus, which has been called BRCA1, has been narrowed to a 3-4 cM interval defined by THRA1, the thyroid hormone receptor locus alpha, and D17S183, an anonymous microsatellite polymorphism. Loci other than BRCA1 that have been identified appear not only to predispose to breast and/or ovarian tumors, but to tumors at other sites too. A new locus has been identified on chromosome 2 which is linked to hereditary non-polyposis colorectal cancer (HNPCC). Families with HNPCC are also at risk of endometrial cancer and tumors of the ovary, amongst other cancer sites. Finally, mutations in the p53 gene are inherited in families with Li-Fraumeni syndrome, a rare cancer syndrome predisposing to breast tumors, sarcomas, leukemia and other cancers. Li-Fraumeni syndrome is also the only inherited cancer syndrome that predisposes at least in part to breast cancer where the actual predisposing gene is known. For the other cancer syndromes, the cloning of the predisposing genes is eagerly awaited.
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PMID:Predisposing genes in breast and ovarian cancer: an overview. 811 68

The inactivation of the tumor suppressor gene p53 has been demonstrated in a variety of human tumors. Herein, we performed a p53 gene analysis of human gynecologic tumor cell lines and tumor tissues. In the SK-OV-3 cell line, Southern analysis suggested the presence of sequence deletions/rearrangements in at least one allele of p53 gene. Transcripts were not detectable by either Northern or PCR analysis. Sequencing analysis of the entire coding region revealed mutations changing the p53 amino acid composition in all six endometrial carcinoma cell lines tested (Ishikawa, Hec1-A, Hec1-B, KLE, RL95-2, and AN-3), and four cell lines in ovarian carcinoma cell lines (Caov-3, -4, OVCAR-3, and Kuramochi). Of the seven cervical carcinoma cell lines, two (HT-3 and C-33A) contained p53 codon changes. We were unable to detect the human papilloma virus (HPV) in these two cell lines. By contrast, five HPV-positive cervical carcinoma cell lines (HeLa S-3, Caski, SiHa, C-41, and ME-180) contained wild-type p53 gene sequences. Examination of loss of heterozygosity (LOH) by PCR revealed that about 30% of the human ovarian carcinoma tissues has LOH at the locus of p53 gene. We suggest that, in the HPV-positive cervical tumors, p53 inactivation occurred via the known mechanism of viral E6/cellular p53 protein association, whereas in all other tumors (ovarian carcinoma, endometrial carcinoma, HPV-negative cervical carcinoma) p53 function was compromised by changes in the amino acid sequence.
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PMID:[Analysis of p53 gene in gynecologic tumors]. 815 58

Mutations of the tumour suppressor p53 gene have been reported in a variety of human malignant tumours, and are frequently associated with over-expression of p53 protein. To examine the significance of p53 gene alteration in endometrial carcinomas, we studied the immunohistochemical reactivity with a monoclonal antibody against p53 (PAb 1801) in 30 endometrial carcinomas as well as in 64 normal endometria. The presence or absence of correlation of p53 over-expression with the clinicopathological features and with the immunohistochemical expression of sex steroid receptors (oestrogen receptors; ER, progesterone receptors; PR) was also analysed. Expression of p53 was found in none of 64 normal endometria, but was identified in 5 of the 30 (16.7%) endometrial carcinomas. All 5 of the p53-positive tumours developed in women more than 3 years post-menopause, whereas the carcinomas in 5 pre-menopausal women and 3 women less than 3 years post-menopause were p53-negative. None of the 5 p53-positive carcinomas was associated with adjacent endometrial hyperplasia. Two of the 5 p53-positive tumours showed non-endometrioid histology: serous papillary and clear cell carcinomas. In contrast, 6 carcinomas accompanied by adjacent hyperplasia were p53-negative. In addition, ER and/or PR expression was found in none of the 5 p53-positive tumours, but was present in 21 of the 25 p53-negative tumours (p < 0.01). These clinicopathological features of p53-positive carcinomas and the inverse correlation of p53 immunoreactivity with sex steroid receptor status suggest that p53 over-expression is frequent in a specific category of endometrial carcinoma, presumably oestrogen-unrelated tumours.
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PMID:Immunohistochemical analysis of p53 protein over-expression in endometrial carcinomas: inverse correlation with sex steroid receptor status. 823 23

Paraffin-embedded materials obtained from 117 cases of endometrial hyperplasia and 84 cases of carcinoma were used for measurement of both ki-ras and p53 gene mutation and aromatase (ARO) and TGF-alpha immunostaining. The overall incidence of ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%). None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in 3 (13.3%) endometrial carcinomas. The intensity of both ARO and TGF-alpha immunostaining was increased in glands of both hyperplasia and carcinoma, and also in the interstitium of carcinoma. The positive sites of both ARO and TGF-alpha were almost the same, with an incidence below 40% in both hyperplasias and carcinomas. The cultured cells of endometrial carcinoma showed aromatase activity below MCF-7 cells, because testosterone was converted to estradiol (E2). TGF-alpha induced cell growth with at an optimal concentration. In HEC-59 cells, TGF-alpha increased both ARO-activity and mRNA. Some promoters on ARO-exon 1 in HEC-59 cells were different from those in BeWo cells. Progesterone inhibited the E2-induced excretion of pre TGF-alpha in endometrial carcinoma cells. These findings suggest that endometrial hyperplasia can be a premalignant condition of carcinoma, and can be initiated by both ki-ras codon 12 mutation and abnormal activity of ARO induced by TGF-alpha. In addition, HEC-59 cells may possess autocrine/paracrine properties involving ARO, E2 and TGF-alpha.
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PMID:[Aromatase activities of endometrial carcinomas and both basic and clinical analyses of endometrial hyperplasia as a premalignant disease]. 837 Oct 7


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