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

The usefulness of prognostic factors in gynecological cancer was evaluated using the oncogenes, tumor suppressor genes and DNA viruses detected with the molecular biological technique. In uterine cervical cancer, HPV types 16 and 18 are considered to have a high oncogenic risk, and are commonly associated with high grade CIN and invasive cancer under persistent HPV infection. C-myc overexpression in advanced stage and p53 mutation in HPV negative case are associated with poor survival. In endometrial cancer, oncogene activation and expression are less frequent than in cervical and ovarian cancer. K-ras point mutation (codon 12) tumors are more aggressive and c-erbB-2 overexpression are associated with metastasis and poor survival. In ovarian cancer, there are numerous abnormalities of oncogenes and tumor suppressor genes. Especially, EGF-R and PDGF-R alpha expression are associated with decreased survival. p53 mutation also decreases survival and response to chemotherapy. Recently. MSH2 (Lynch II syndrome) and BRCA1 gene are known to relate with familial ovarian cancer.
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PMID:[Evaluation of prognostic factors in gynecological cancer examined by molecular biological study]. 868 14

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

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

I have investigated 84 endometrial specimens (from 15 cases of normal endometrium, 20 cass of hyperplasia and 49 cases of endometrial carcinoma) to determine the relationship between three proteins (proliferating cell nuclear antigen (PCNA), p53 gene product and c-erB-2 gene product) and endometrial carcinoma by immuno-histochemical staining. In 49 cases of endometrial carcinoma, the positive rates for PCNA, p53 protein (mutant type) and c-erbB-2 protein were 65.3%, 59.2% and 22.4%. I could not find the expression of p53 protein besides endometrial carcinoma. And I could find the expression of c-erbB-2 protein in 11 cases of endometrial carcinoma and 1 case of atypical hyperplasia, but not in normal endometrium. p53 protein was more common in such a case, as with lymphnode metastasis, deep myometral invasion and undifferentiated adenocarcinoma. c-erbB-2 was also more common in a case with deep myometrial invasion. In conclusion, PCNA, p53 protein and c-erbB-2 protein are related to the proliferation of endometrial carcinoma. So they can be useful factors in making the prognosis.
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PMID:[Immunohistochemical study of PCNA, p53 gene product and c-erbB-2 gene product in endometrial carcinoma]. 893 11

Prognostic factors capable of detecting potential for aggressive disease in early stage endometrial cancer might be useful in selecting patients for early adjuvant therapy. Sixty-three patients with surgical Stage I endometrial carcinoma treated by hysterectomy with a mean follow-up of 55 months were evaluated for tumor type, grade, depth of myometrial invasion, presence of vascular invasion, DNA ploidy, and HER-2/neu overexpression by immunohistochemical techniques. These results were compared with HER-2/neu gene amplifications evaluated by fluorescence in situ hybridization (FISH) and their ability to predict disease survival. For FISH, sections 5 microns thick of formalin-fixed, paraffin-embedded tissues were processed using the Oncor Chromosome In Situ Hybridization System. Automated hybridization using the Ventana Gen was performed with the Oncor unique sequence digoxigenin-labeled HER-2/neu DNA probe. Gene copy numbers were evaluated using the Zeiss Axioskop50 fluorescence microscope. HER-2/neu amplification was noted in 24 (38%) of 63 cases. By multivariate analysis, only aneuploidy (P = .04) and HER-2/neu amplification by FISH (P = .04) independently correlated with survival. Although we saw a relationship between HER-2/neu protein expression and gene amplification, this trend did not achieve statistical significance. HER-2/neu oncogene amplification can be assessed using automated FISH on formalin-fixed, paraffin-embedded tissue. HER-2/ neu amplification predicts poor outcome in Stage I endometrial cancer. HER-2/neu amplification status has potential use in the identification of patients with high risk of disease recurrence who might benefit from intensified therapy.
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PMID:Identification of HER-2/neu oncogene amplification by fluorescence in situ hybridization in stage I endometrial carcinoma. 926 26

Expression of the HER-2/neu proto-oncogene product was looked for immunohistochemically in 222 endometrial carcinomas in a retrospective follow-up study. The intensity of protein expression was correlated with patient survival. Median follow-up time was 4.8 years. In 109 (49%) of 222 endometrial carcinomas there was aberrant expression of HER-2/neu. HER-2/neu-expression did not correlate with p53-expression and proliferation rate, as determined immunohistochemically by the monoclonal antibody Ki-S1. In univariate statistical analysis aberrant HER-2/neu expression was not predictive of adjusted survival (p = 0.18) and of disease-free survival (p = 0.42). In multivariate analysis HER-2/neu-expression was not found to be an independent prognosticator (p = 0.099) as compared to FIGO-stage (p = 0.0001), histologic grade (p = 0.00099) and proliferation rate (p = 0.0013). Therefore immunohistochemically detected expression of HER-2/neu seems not to be a clinical prognosticator in endometrial cancer.
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PMID:Immunohistochemically detected HER-2/neu-expression and prognosis in endometrial carcinoma. 927 38

HER-2/neu oncogene is believed to be involved in tumorigenesis of several human malignancies. To assess the pattern of expression of this oncogene in normal, hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to paraffin-embedded tissue sections obtained from 146 patients with endometrial adenocarcinoma. A spectrum of hyperplastic changes ranging from simple hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases. Expression for HER-2/neu oncogene was demonstrated as cell membrane staining. Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous expression for HER-2/neu oncogene. The intensity of the immunostaining and the number of cells stained for HER-2/neu oncogene had no significant association with surgical stage or histologic grade, although the proportion of patients demonstrating overexpression increased significantly as the histologic grade of their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a statistically significant correlation was found between the level of expression of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated that HER-2/neu oncogene expression is variably present in normal and hyperplastic endometrium. Association between HER-2/neu oncogene expression, higher grade lesions and poor survival in patients with endometrial cancer may also justify assessment of HER-2/neu oncogene as a reliable prognostic indicator.
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PMID:Expression of HER-2/neu oncogene in normal, hyperplastic, and malignant endometrium. 964 53

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

HER-2/neu is a proto-oncogene associated with poor prognosis in women with breast and ovarian carcinoma. The significance of HER-2/neu in endometrial carcinoma is less clearly established. The authors compared HER-2/neu gene amplification using fluorescence in situ hybridization and protein overexpression using immunohistochemistry with survival in patients with endometrial carcinoma. Fluorescence in situ hybridization and immunohistochemical staining were performed on 72 formalin-fixed, paraffin-embedded endometrial carcinoma specimens. Vysis combination HER-2/neu and centromere 17 probe mixture was applied to isolated tumor cell nuclei. A minimum of 200 nuclei were scored for each specimen using standard signal enumeration criteria. A specimen was considered amplified with 5% or greater amplified nuclei. Tissue sections were immunostained with polyclonal antibody against p185erb-2 transmembrane glycoprotein. Immunohistochemical reactivity was scored on a three-tiered scale. HER-2/neu gene amplification and protein overexpression were detected in 15 of 72 (21%) and 12 of 72 (17%) of the specimens, respectively, with 2 cases of normal copy overexpression and 5 cases of amplification without overexpression. Both amplification and overexpression were associated with higher grade tumors. Amplification was associated with clear cell and serous subtypes (p = 0.002), and overexpression with only clear cell type (p = 0.006). Using the proportional hazards model of survival, amplification was found to have significant negative predictive value beyond stage, grade, and cell type (p = 0.002). HER-2/neu gene amplification as detected by fluorescence in situ hybridization in archival material has significant prognostic value.
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PMID:HER-2/neu amplification and overexpression in endometrial carcinoma. 1020 71


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