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

Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found in human malignancies, we examined the hypothesis that p53 mutations occur in human endometrial carcinoma. Sequencing analysis of exons 5-8 revealed point mutations in 3 of 21 (14%) tumors; one mutation was an unusual single-base insertion at codons 176-177, resulting in a premature stop codon, whereas the other two were CGG----TGG transitions at codon 248. Two of these tumors showed reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. These data indicate that p53 mutations occur in human endometrial carcinoma, although relatively infrequently, and that loss of the normal p53 allele does not necessarily occur with point mutation of the p53 gene in this tumor type.
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PMID:p53 gene mutations in human endometrial carcinoma. 149

The inactivation of the tumor suppressor gene p53 has been demonstrated in a variety of human tumors. In this study, we present a p53 gene analysis of 13 uterine carcinoma cell lines. Sequencing analysis of the entire coding region revealed mutations changing the p53 amino acid composition in all six endometrial carcinoma cell lines tested (Ishikawa, Hecl-A, Hecl-B, KLE, RL95-2, and AN-3). Of the seven cervical carcinoma cell lines, two (HT-3 and C-33A) contained p53 codon changes as well. We were unable to detect human papillomavirus in these two cell lines. By contrast, five human papillomavirus-positive cervical carcinoma cell lines (HeLa S-3, Caski, SiHa, C-4I, and ME-180) contained wild-type p53 gene sequences. We suggest that, in the human papillomavirus-positive cervical tumors, p53 inactivation occurred via the known mechanism of viral E6/cellular p53 protein association, whereas in all other tumors p53 function was compromised by changes in the amino acid sequence.
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PMID:Analysis of the p53 gene in human uterine carcinoma cell lines. 166 Mar 40

To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at 27 loci on 10 different chromosomes, i.e., chromosomes 1, 3, 6, 11, 13, 15, 17, 18, 20, and 21, but was not detected at loci on chromosomes 4, 5, 7, 9, 10, 12, 14, 16, and X. It was observed only in seven of 24 cases, and the other 19 cases did not show LOH at any loci examined, including five cases of tumors with a high proportion of adenomatous hyperplasia. Among seven tumors with LOH at one or more loci, five tumors showed LOH at loci on the short arm of chromosome 17. Furthermore, mutations of the p53 gene, which is located on the short arm of chromosome 17, were detected in three of these 24 tumors by a polymerase chain reaction-single strand conformation polymorphism analysis and subsequent DNA sequencing. In two of these three tumors, p53 mutations were accompanied by the loss of wild-type p53 alleles. These results suggest that inactivation of the p53 gene is involved in the development of EC as in the case of several other types of human cancers.
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PMID:Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus. 191 80

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome. Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer. In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER-2/neu gene copy number, and immunohistochemistry was used to characterize expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as showing moderate or high immunostaining. HER-2/neu gene amplification was detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases. Fourteen of these cases showed both moderate or high immunostaining and gene amplification. Clinical follow-up information was available for 76 women in this study. Women whose endometrial cancer exhibited HER-2/neu gene amplification by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with moderate or high HER-2/neu immunostaining were associated with a lower cumulative overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001). Multivariate analysis of survival rates revealed HER-2/neu overexpression to be an independent predictor of overall survival (P = 0.0163). Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039). However, among those women whose tumor lacked overexpression, overall survival was not improved by adjuvant treatment.
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PMID:Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival. 758 56

Germ line mutations of the p53 gene have been described in the Li-Fraumeni Cancer Family Syndrome and occur in patients with multifocal gliomas, particularly those with a history of a metachronous cancer or a family history of cancer. p53 dysfunction is often associated with ovarian cancer. Patients with ovarian carcinoma frequently develop synchronous or metachronous cancers and may have a family history of this or related cancers. Thus, we hypothesized that germ line p53 mutations might be associated with a significant proportion of ovarian cancers. Germ line DNA isolated from peripheral leukocytes of 73 patients with ovarian carcinoma was screened for p53 sequence abnormalities utilizing single-strand conformation polymorphism analysis and direct PCR sequencing techniques. As many as 40% of this cohort of ovarian cancer patients from 67 families may represent familial phenotypes. Synchronous and metachronous cancers occurred in 19% of the cohort. Only two intron-based polymorphisms were found. Neither has been previously reported. One of these, in intron 6, occurred in three unrelated patients all of whom had a history of metachronous breast cancer. A polymorphism in intron 10 occurred in a patient with synchronous endometrial cancer. No classic germ line mutations of p53 were found.
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PMID:Absence of significant germ line p53 mutations in ovarian cancer patients. 767 3

Uterine papillary serous adenocarcinoma (UPSC) is one of the most aggressive endometrial tumors. UPSC has been associated with an increased propensity for extrauterine spread. Survival rates of not more than 50% are commonly reported even for tumors which appear to be confined to the uterus. Small areas of UPSC can be found in otherwise well-differentiated endometrial lesions and yet still determine the overall prognosis. In the present study we evaluated histologic criteria that might be helpful in diagnosing small-volume UPSC, including silver-stained nucleolar organizer regions (AgNOR) which have prognostic importance in a variety of tumors, and nuclear size which has been used for prognostication in endometrial cancer. We examined 25 UPSC specimens and compared them to grade III (GIII, n = 10) and grade I (GI, n = 10) typical endometrial adenocarcinoma using the following parameters: mean AgNOR count per cell was UPSC 6, GIII 6.0, and GI 4.3; mean AgNOR area was UPSC 1.28 microns2, GIII 1.35 microns2, and GI 0.86 microns2; total AgNOR area per cell was UPSC 7.5 microns2, GIII 8.13 microns2, GI 4.47 microns2; and nuclear size was UPSC 66.9 microns2, GIII 60.3 microns2, GI 34.8 microns2. All differences between UPSC or GIII tumors and GI lesions were statistically significant. Overexpression of p53, as determined histochemically, was seen in 64% of the UPSC specimens. UPSC is characterized by high AgNOR count and area per cell, large nuclear size, and a high rate of p53 overexpression. Evaluation of these parameters in biopsy material may aid in selecting high-risk patients for adjuvant therapy trials.
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PMID:Histologic characterization of uterine papillary serous adenocarcinoma. 770 79

The authors previously reported a significant frequency of activating point mutations in codon 12 and 13 of the K-ras gene in endometrial carcinoma and endometrial atypical hyperplasia from Osaka, Japan. They also showed that alterations of the p53 gene are found frequently in those tumors. This study was designed to reveal possible demographic differences in the prevalence of K-ras and p53 mutations in endometrial carcinoma. Tumor-enriched areas of paraffin-embedded histologic sections obtained through the Colorado Central Cancer Registry were isolated and extracted for DNA. Fragments amplified by polymerase chain reaction (PCR) were screened for transforming mutations in codon 12, 13, or 59-63 of K-ras by direct sequencing. Of 38 endometrial adenocarcinomas that were analyzed, K-ras activation was detected in 4 cases (11%), three in codon 12 (a single case with a GGT-->AGT transition, a single case with a GGT-->GAT transition, and a single case with a GGT-->TGT transversion) and one in codon 13 (a GGC-->GAC mutation). The prevalence of K-ras mutations was significantly lower in endometrial carcinomas from Colorado (4 of 38, 11%) than in those from Osaka, Japan (17 of 57, 31%; P = .02). Mutations in exons 5-8 of p53 were screened by PCR-SSCP analysis, and subsequently confirmed by direct sequencing. Mutations in the p53 gene were detected in 5 of 38 endometrial carcinomas from Colorado (13%), including a single base substitution mutation in 3 cases (60%) and a deletion mutation in 2 cases (40%). Mutations in the p53 gene were significantly more frequently found in G3 cancers (3 of 7, 43%) than G1-G2 cancers combined (2 of 31, 6%; P = .025). Although the prevalence of p53 mutations in endometrial carcinomas from Colorado was not significantly different compared to that from Osaka, Japan (9 of 40, 23%), a G:C-->A:T transition at a CpG site, which was the most common base substitution mutation among Japanese, was not included in any tumors from Colorado. A rare polymorphism in codon 213 (CGA-->CGG) was observed in three cases. These observations may indicate that genetic or environmental factors may significantly influence the pathway of endometrial carcinogenesis.
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PMID:Alteration of the p53 tumor suppressor gene and activation of c-K-ras-2 protooncogene in endometrial adenocarcinoma from Colorado. 785 67

Expression of four biologic markers was studied in 69 cases of endometrial cancer to identify their association with cell type, decreased survival, and increased tumor metastasis. Cell types included endometrioid (n = 45), serous papillary (n = 16), and clear cell (n = 8). Immunohistochemical stains were employed to detect the presence of epidermal growth factor receptor (EGFR), HER-2/neu, p53, and proliferating cell nuclear antigen (PCNA). Analysis revealed that EGFR was expressed in 49%, HER-2/neu in 59%, p53 in 9%, and PCNA in 16% of tumor specimens. HER-2/neu overexpression was significantly associated with depth of myometrial invasion. p53 and PCNA immunoreactivity significantly correlated with nonendometrioid histology, although PCNA was less specific in labeling these less favorable cell types. EGFR immunoreactivity also significantly correlated with nonendometrioid cell types and tumor metastases at time of diagnosis. Seventy-seven percent of patients with metastatic disease were EGFR-positive versus 36% positivity in patients with no evidence of metastases (P < 0.002). For patients with endometrioid adenocarcinoma, evidence of EGFR overexpression decreased survival from 89 to 69% (P < 0.04). In the serous papillary and clear cell category, EGFR positivity decreased survival from 86 to 27% (P < 0.03). EGFR strongly correlates with tumor metastasis and patient survival in endometrial cancer. Altered expression of this oncoprotein may serve as a guide to prognosis and treatment in these patients.
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PMID:Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. 790 88

Ten human endometrial adenocarcinoma grafts were subsequently transplanted from an original tumour growing in nude mice for several years and nine were investigated for cell proliferation, tumour volume growth, allele imbalance and protein products of Rb and p53 suppressor genes to study a possible inherited connection between these factors. We did not find faster tumour volume growth in tumours with increased cell proliferation, in contrast to melanomas and breast cancers growing in nude mice. We concluded that a probably existing link between mechanisms regulating cell proliferation and cell loss in these two tumours does not operate in endometrial carcinoma as measured by us. The tumour progression may be one important factor which influences mechanisms regulating cell proliferation and cell loss.
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PMID:Tumor volume growth and cell proliferation in an estradiol resistant human endometrial adenocarcinoma growing in nude mice. 791 31

Abnormal expression of p53, transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), and c-erbB-2 occurs in a variety of cancers and in some cases is associated with poor prognosis. Immunoperoxidase staining using these markers in formalin-fixed, paraffin-embedded endometrial carcinoma tissue was performed to determine whether immunoreactivity correlates with survival and known prognostic variables. Cases included 84 endometrioid adenocarcinomas, five adenoacanthomas, 12 adenosquamous carcinomas, 11 serous carcinomas, 15 clear cell carcinomas, and one carcinosarcoma for a total of 128 cases. Frequencies of immunoreactivity were as follows: p53, 37 of 128 (29%); TGF alpha, strong (2+) 23 of 128 (18%) and intermediate (1+) 26 of 128 (20%); EGFR, strong (3+) 21 of 128 (16%) and intermediate (2+ or 1+) 83 of 128 (65%); and c-erbB-2, strong (2+) four of 128 (2%) and intermediate (1+) three of 128 (1%). p53 and TGF alpha staining showed statistically significant correlations with decreased length of survival (P < .0017 and P < .0013, respectively, generalized Savage [Mantel Cox]). p53 immunoreactivity correlated with tumor types, grade, and stage. Transforming growth factor alpha staining correlated with increased depth of invasion and presence of vascular invasion. Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables. c-erbB-2 staining correlated with tumor type. In the multivariate analysis p53 and TGF alpha staining were not independent predictors of survival when other variables were taken into account, including grade, stage, tumor type, presence of vascular invasion, and depth of invasion. Grade and stage were the only independent predictors of survival when used in combination in a Cox proportional hazards model.
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PMID:Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. 792 13


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