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

Heat shock proteins HSP70 and HSP90 are sex steroid receptor-associated proteins, and HSP90 expression has reportedly been correlated with sex steroid receptor status in endometrial carcinomas. HSP70 is also known to associate with several oncogene products such as p53 protein, and expression of HSP70 has been reported to be a prognostic factor in several malignant neoplasms. In endometrial carcinomas, however, little is known about the prognostic significance of these proteins. Therefore, we analyzed the survival of 44 endometrial carcinoma patients treated in our hospital with reference to the immunohistochemical expressions of HSP70 and HSP90, as well as the clinicopathological factors such as age, menstrual status, FIGO stage, histologic grade, p53 protein overexpression, and sex steroid receptor status. The expression of HSP70 was observed in 50% (22 cases), and strong HSP90 expression in 30% (13 cases) of the 44 carcinomas. The patients with HSP70-positive tumors showed significantly poorer survival than the patients with HSP70-negative tumors (p = 0.045), although multivariate analysis did not reveal HSP70 expression to be an independent prognostic factor. In contrast, the strong expression of HSP90 in the tumor was significantly correlated with a favorable prognosis of the patient (p = 0.026). Other prognostic indicators were FIGO stage (p = 0.0086) and the expression of progesterone receptor (p = 0.042). Accordingly, expressions of HSP70 and HSP90 each have different prognostic significance in endometrial carcinoma and may be useful for prediction of patient survival.
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PMID:Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. 982 79

Uterine papillary serous carcinoma (UPSC) is a biologically aggressive carcinoma that causes a disproportionate number of endometrial cancer deaths because of its dismal clinical outcome. Although the precursor lesion of UPSC has been suggested both morphologically and molecularly, diagnosis continues to represent a challenge to surgical pathologists, particularly in biopsy specimens, largely in part because of its multiple histologic patterns and many benign morphologic mimics. In this study, we used p53 immunohistochemical staining as an adjunct test to correctly identify six cases of uterine surface carcinoma (USC) prospectively and three cases retrospectively. Both sensitivity and specificity for this immunostaining method approached 100% when the cutoff score of p53 overexpression was 7 or higher. The precision estimated by receiving operating characteristic curve was 100%, indicating that the diagnostic value of the score for p53 overexpression was very high. p53 immunohistochemical staining was considered a significant adjunct diagnostic method for the probable precursor lesion of UPSC. The probable precursor lesion of UPSC, previously referred to as endometrial intraepithelial carcinoma or endometrial carcinoma in situ, appears to represent the early phase of UPSC. However, unlike its names would suggest, this lesion is often multicentric and behaves in a more aggressive fashion than regular in situ carcinomas. For this reason, we prefer the term uterine surface carcinoma, a term that is more descriptive and less restrictive, to emphasize the unique aggressive nature of the UPSC precursor lesion. The reason we postulate using the term uterine surface carcinoma rather than endometrial intraepithelial carcinoma or endometrial carcinoma in situ is that the latter terms would seem define a neoplastic process confined to the endometrial epithelium without potential for metastasis. In reality, the precursor lesion of UPSC has a tendency to stromal and vascular space involvement as seen by the presence of stromal and vascular invasion in one of the prospectively identified USC cases. Therefore, the term uterine surface carcinoma is selected to alert clinicians that this early carcinoma has features of carcinoma in situ, but still carries a potential for metastasis.
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PMID:p53 immunostaining as a significant adjunct diagnostic method for uterine surface carcinoma: precursor of uterine papillary serous carcinoma. 985 Jan 72

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

The prognostic value of p53 protein overexpression was investigated in a large series of early stage endometrial carcinomas with long follow-up (n=179, median follow-up 147 months). P53 overexpression was detected in 10 cases (5.6%). At the end of the study period, 30% (3/10) of patients with p53 protein overexpression had died of their disease compared to 6.5% (11/169) of those without overexpression. Multivariate analysis revealed that only myometrial invasion (RR 2. 1; 95% CI=1.2-3.6; P=0.001) and p53 overexpression (RR 9.5; 95% CI=2. 5-36.8; P=0.007) were independent predictors of survival. These results suggest that immunohistochemical evaluation of p53 protein overexpression provides strong prognostic information for the outcome of endometrial carcinoma patients with early stage disease.
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PMID:p53 protein overexpression is a prognostic indicator of poor survival in stage I endometrial carcinoma. 986 26

The p53 gene is frequently mutated in various human tumors. Polymorphism is an additional genetic alteration observed in exons and introns of the p53 gene of normal tissues and tumors. Distributions of alleles of three common polymorphisms of the p53 gene; a 16 bp duplication in intron 3, codon 72 of exon 4 and a sequence in intron 6, were studied in peripheral white blood cells (WBC) of patients with ovarian or endometrial carcinomas. The analysis was performed by PCR and direct sequencing. The 100% linkage observed between the most common haplotypes of each polymorphism in healthy subjects was lower in the patients. A significant difference was observed between frequencies of genotype and haplotype combinations in patients with ovarian carcinoma and endometrial carcinoma. The incidence of heterozygosity was increased in ovarian carcinoma and decreased in endometrial carcinoma. Our results suggest that the p53 gene may be involved in susceptibility and predisposition to various cancers not only by mutations but also by preferential presentation of polymorphic alleles.
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PMID:Polymorphisms of the p53 gene in women with ovarian or endometrial carcinoma. 986 27

Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
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PMID:Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer. 989 67

bcl-2 expression was examined on paraffin-embedded specimens in proliferative, hyperplastic, and neoplastic human endometrium by immunohistochemistry. The results of bcl-2 immunostaining in endometrial carcinomas were compared with clinicopathological indicators as well as with p53 accumulation. The streptavidin-peroxidase detection system was used and the intensity and the distribution of immunostaining was evaluated semiquantitatively by counting H-score values. Expression of the bcl-2 protein was found in 2 out of 5 cases of proliferative endometrium (mean H-score 0.4, range 0.35-0.45), 4 out of 5 cases of simple hyperplasia (mean H-score 1.23; range 1.0-1.4), 4 out of 5 cases of complex hyperplasia (mean H-score 1.1; range 0.7-1.2) and in 7 out of 25 cases of endometrial carcinoma (mean H-score 0.48; range 0.35-0.65). All bcl-2 positive slides were obtained from patients who had endometrial cancer and who were in the early (stage I due to FIGO) clinical stage of the disease. bcl-2 expression was not related to age, surgical stage or histopathological features, and neither was there an inverse correlation between bcl-2 immunostaining and p53 expression reported in the study of neoplastic endometrium. Our data indicate that mechanisms other than p53 may play a role in the regulation of bcl-2 expression in endometrial carcinomas.
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PMID:bcl-2 protein expression in endometrial carcinoma: the lack of correlation with p53. 992 61

The WAF1 protein, which is a downstream mediator of p53, functions as a universal inhibitor of cyclin-dependent kinases. The functional link between p53 and WAF1 suggests the possibility that alteration in WAF1 function constitutes an alternative mechanism to p53 inactivation. However, there are few reports describing somatic mutations of the WAF1 gene in various human malignancies. A polymorphism in the WAF1 gene, a C-to-A transversion at codon 31 resulting in the change of a serine (Ser) to an arginine (Arg), is well known. We found this substitution in 42 of 54 endometrial carcinoma patients. Allele frequency was 0.44/0.56 for the codon 31 polymorphism (Ser/Arg), the difference of allele frequency between patients and normal controls being significant (0.59/0.41 in normal controls). In addition, individuals carrying the codon 31 Arg allele had a tendency to develop histologically high-grade (odds ratio, 6. 11) and clinically advanced tumors. We investigated the association of the Arg allele with the known risk factors of endometrial carcinomas. Statistical analyses of 42 cases and 32 controls carrying the codon 31 Arg allele identified hypertension (odds ratio, 4.33) and family history of cancer (odds ratio, 2.81) as positive risk factors. This implies that these two parameters may be associated with a tendency to develop endometrial carcinomas in individuals carrying the codon 31 Arg allele of the WAF1 gene.
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PMID:WAF1 genotype and endometrial cancer susceptibility. 1002 Dec 99

The carcinoma of the endometrium is the most common malignancy seen in the female pelvic genital organs. Important risk factors are age and unopposed estrogen (both endogenous and exogenous). In comparison, the association of antiestrogens (e.g., tamoxifen) and endometrial cancer is rather small, as yet. Fortunately, survival is high because the majority of patients have in common the presence of a low grade, low stage carcinoma of the endometroid type which gives rise to vaginal bleeding and forces the patients to attend the gynecologist. Special screening studies (e.g. vaginal sonography) to evaluate the endometrium are not indicated in the asymptomatic patient without risk factors. Tumor type, grading, and--most importantly--the depth of myoinvasion and the extent of extrauterine disease are the prognostic indicators that allow differential treatment, and help to identify patients at high risk vs. low risk for recurrent disease. Investigations of growth fraction, ploidy, steroid receptors, K-ras or p53 may be a supplement for dissecting special subgroups, but do not influence the clinical regimen, as yet. Most patients with stage I cancer are cured by surgery alone. Patients successfully treated for endometrial cancer should enjoy the benefits of estrogen replacement therapy, since they do not bear a risk of increased recurrence of their disease. Radiation therapy will be given to patients with incomplete resection of pelvic disease and/or extensive lymphonodal involvement, especially paraaortal lymph node metastasis. As yet, there is no rationale for an adjuvant hormone-(gestagen-) or chemotherapy. An exception, however, is the (mostly palliative) treatment of recurrent disease.
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PMID:[Algorithm of clinical aspects and pathology of endometrial carcinoma]. 1009 Dec 34

Overexpression and mutation of p53 in 46 primary endometrial carcinomas were determined comparatively with the status for estrogen receptor (ER) and progesterone receptor (PR). Immunohistochemically p53 overexpression was found in 9 of 46 cases (20%), while eight kinds of mutations in that gene were detected in 7 of 46 endometrial carcinomas (15%), using polymerase chain reaction single-strand conformation polymorphism and subsequently direct sequencing method. Six of nine cases with p53 overexpression showed p53 mutation. All eight mutations showed single substitutions, and three cases in exon 4, one in exon 5, two in exon 6, and two in exon 7 were found. The cases with the p53 overexpression were significantly inversely related to that of ER or PR staining. Most endometrial carcinoma with p53 overexpression and/or mutation had a relatively poor prognosis and showed no reactivities of ER or PR.
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PMID:p53 overexpression and mutation in endometrial carcinoma: inverted relation with estrogen and progesterone receptor status. 1010 96


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