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

Expression of a c-myc proto-oncogene product known as p62 (c-myc) was studied in 18 cases of stage I endometrioid (typical) adenocarcinoma of the uterus by immunohistochemistry and correlated with mucin production and other pathologic features. Cytoplasmic staining of tumor cells for c-myc product was seen in all cases and nuclear staining in three cases. Endometrial stromal cells were invariably negative and myometrial nuclear staining was seen in three cases. Within the tumor itself, whereas intense staining was frequent in high grade tumors with deep myometrial and vascular invasion, faint to moderate staining was frequent in well differentiated tumors with superficial myometrial invasion. A general tendency was also seen for greater staining in the myometrial component of the tumor than in tumor located in the endometrium. Whereas staining in the latter was frequently patchy in distribution, c-myc expression was invariably uniform in the myometrial component. Mucin production was somewhat greater in endometrial than myometrial components but did not correlate with c-myc expression or other pathologic features. This study demonstrates that c-myc is variably expressed in endometrial carcinoma and high c-myc expression can be associated with populations of tumor cells selectively capable of myometrial and vascular invasion.
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PMID:C-myc gene expression in stage I endometrioid adenocarcinoma of the uterus. 130 72

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
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PMID:Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells. 137 Feb 27

Marked changes in both growth factor and proto-oncogene expression occur due to treatment of hormonally-responsive human cancers with progestins and antiestrogens. In human endometrial cancer cell lines the antiproliferative effects of progestins and antiestrogens in a particular cell line appear to be associated with similar effects on growth factor and/or proto-oncogene expression. This suggests that although these compounds initially interact with different steroid hormone receptors, the molecular mechanisms of their growth inhibition may be essentially similar. In the case of human breast cancer cell lines, however, the effects of progestins and antiestrogens on gene regulation are often different, suggesting that the molecular mechanisms of progestin and antiestrogen growth inhibition may be essentially dissimilar.
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PMID:Mechanisms of growth inhibition by antiestrogens and progestins in human breast and endometrial cancer cells. 152 52

A chromosome study was performed in a recurrent endometrial cancer. The cytogenetic analysis performed with a quinacrine-Hoechst banding technique revealed rearrangements of chromosomes #1 and #11 [i.e.: der(11),t(1;11)(q21;q23)], which was found in all metaphases. In addition, a deletion of chromosome 6(q21), trisomy of chromosomes #7 and #10, monosomy X, and -4 as the clonal changes. Partial trisomy for a long arm of chromosome #1 also was observed in almost all analyzed metaphases (11 of 12 cells). These data showed the association of rearrangement of 1q in endometrial cancer and/or redevelopment of tumor, and also suggest the possible participation of chromosome #11 on which the human proto-oncogene c-ets was mapped.
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PMID:Recurrent endometrial adenocarcinoma with rearrangement of chromosomes 1 and 11. 394 58

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.
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PMID:Growth factor expression in normal peritoneum of patients with gynecologic carcinoma. 795 83

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

Mutations involving the K-ras proto-oncogene are believed to play an important role in the mechanism of tumorigenesis for many human cancers and occur in 10-30% of endometrial carcinomas. In the present study 221 cases of endometrioid endometrial carcinoma obtained from Japanese patients with average follow-up of 41 months were examined for point mutations in codon 12 of K-ras through use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-ras mutations were significantly associated with the presence of lymph node metastases (P < 0.04). Since endometrial carcinoma in premenopausal women generally behaves less aggressively than tumors of similar histologic grade arising in postmenopausal patients, we evaluated the effect of K-ras mutation on outcome in patients stratified into three different age categories (<53 years, premenopausal; 54-59 years, perimenopausal; >60 years, postmenopausal). In the postmenopausal age group (>60 years), the presence of K-ras mutations was statistically significantly associated with patients who died or experienced recurrence (41.2% vs 13.0%; P < 0.03). This was related to a dramatic (greater than eightfold; P = 0.011) increase in the likelihood of adverse outcome between the premenopausal and postmenopausal states for patients whose tumors contained mutant K-ras. These findings point to a possible role for K-ras activation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.
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PMID:K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient. 891 Jun 34

Growth factor regulation of normal and cancerous cell proliferation has been well-documented and may be mediated by proto-oncogene activity. The purpose of this study was to assess changes in proliferation and mitogen-induced c-fos mRNA expression of an endometrial carcinoma cell line, HEC-1-A, in response to TGF-beta, a potent growth-inhibitory peptide. HEC-1-A cells were incubated in the presence or absence of TGF-beta. Mitogen-stimulated cells were additionally treated with epidermal growth factor (EGF). Changes in proliferation were measured by [3H]thymidine uptake assays. Alterations in EGF-induced c-fos expression following TGF-beta pretreatment were assessed by Northern blot using a 32P-labeled human c-fos probe. Finally, chloramphenicol acetyltransferase assays were performed to evaluate c-fos promoter activity in response to treatment conditions. Basal and EGF-stimulated proliferation was inhibited by TGF-beta in a dose- and time-dependent manner. TGF-beta also reversibly decreased EGF-induced c-fos mRNA expression in a dose- and time-dependent manner. Sequences in the c-fos promoter that were stimulated by EGF showed suppressed activity when preincubated with TGF-beta. These results show that TGF-beta negatively modulates EGF-induced c-fos expression, which may be related to the observed inhibition of carcinoma cell proliferation.
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PMID:Transforming growth factor-beta negatively modulates proliferation and c-fos expression of the human endometrial adenocarcinoma cell line HEC-1-A. 910 92

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

Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.
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PMID:The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. 981 87


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