Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

The aim of this study was to perform a clinical and immunohistochemical comparison between simultaneous independent tumors involving endometrium and ovary and metastatic endometrial tumors, and to try to find clinical and /or immunohistochemical parameters differentiating between these two entities. Sixteen cases of simultaneous independent primaries of endometrium and ovary, presenting the same histologic type, were compared with 12 cases of primary endometrial cancer, demonstrating ovarian metastases. The comparison related to patients' characteristics and immunohistochemical expression of estrogen and progesterone receptors (ER,PR), bcl-2, HER-2 /neu, p53, and cell proliferation marker Ki-67 in endometrial and ovarian tumors. The only clinical parameter differentiating significantly between the groups was the prevalence of familial cancer, being more frequent in the group of metastatic tumors (P = 0.03). Immunohistochemical analysis demonstrated the same immunostaining in endometrium and ovary for all immunohistochemical parameters in cases of metastatic endometrial cancer. Conversely, 62.5% of cases with simultaneous tumors of endometrium and ovary could be differentiated from metastatic tumors by distinct immunohistochemical expression of ER and PR in endometrial and ovarian tumors (P = 0.0006), and 31.3% of cases could be differentiated by distinct immunostaining for bcl-2 (P = 0.03). Immunohistochemical parameters HER-2 /neu, p53 and Ki-67 were not appropriate for the distinction between the two study groups. We conclude that the application of immunohistochemical analysis may play an important role in the differentiation between cases of simultaneous independent carcinomas of endometrium and ovary vs. cases of endometrial carcinoma with ovarian metastases.
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PMID:Simultaneous carcinoma of the endometrium and ovary vs endometrial carcinoma with ovarian metastases: a clinical and immunohistochemical determination. 1263 Dec 17

The objective of the present study was to evaluate the correlation between HER-2 gene amplification and HER-2 protein overexpression in endometrial carcinoma using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We also analyzed chromosome 17 aneusomy and the association between these biological parameters and conventional clinicopathological variables. FISH analysis was performed on 73 selected paraffin-embedded sections from endometrial carcinomas which previously had HER-2 status determined immunohistochemically using monoclonal antibodies (MoAb) 300G9 and CB11. Using a ratio of more than two oncogene signals/centromere to indicate amplification, a total of 42 out of the 73 endometrial tumors included in this study resulted positive by FISH where as protein overexpression was identified in 29 out of 73 with a concordance rate of 74.3%. However, when the mean signals/centromere per nucleus increased (ratio > 4 < or = 5) a higher concordance between the two assays was seen (p = 0.007). In addition, HER-2 amplification was significantly correlated with tumor stage (p = 0.021) and myometrial invasion (p = 0.010), whereas chromosome 17 polisomy showed a positive correlation only with myometrial invasion (p = 0.004) No significant correlation was found between HER-2 gene amplification, chromosome 17 aneusomy and patient outcome. Nevertheless, the probability of a 5 year overall survival decreased from 70% to 43%, respectively, for ratio > 2 < or = 4 and ratio > 4 < or = 5 when we grouped the amplified cases on the basis of HER-2:CEP17 ratio. In conclusion, molecular characteristics provide objective data that may be useful in predicting prognosis in patients with endometrial cancer.
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PMID:HER-2/neu oncogene amplification and chromosome 17 aneusomy in endometrial carcinoma: correlation with oncoprotein expression and conventional pathological parameters. 1286 77

The goal of endocrine therapy in breast cancer is to block the action of estrogen on the tumor cells either by inhibiting estrogen from binding to the specific estrogen receptor or by inhibiting its synthesis. Tamoxifen, a selective estrogen receptor modulator, is the standard endocrine treatment for hormone receptor-positive breast cancer, both in the adjuvant and metastatic settings. Tamoxifen inhibits the binding of estrogen to the receptor, resulting in inhibition of hormone action. However, as tamoxifen is also weakly estrogenic, it may not be optimally effective and increases the risk of endometrial cancer and stroke. Furthermore, patients may be refractory or may become resistant to tamoxifen treatment. Since aromatase inhibitors (AI) block the synthesis of estrogen and have no intrinsic estrogenic activity, they have the potential to be more effective than tamoxifen. Their different mechanism of action and chemical structures may also circumvent tamoxifen resistance. Consequently, AIs are currently being evaluated as an alternative to tamoxifen treatment. A preclinical model has recently been developed to compare the efficacy of AIs and antiestrogens in different treatment schemes and to assist in the design of clinical trials. Current studies with the MCF-7Ca xenograft model are exploring the effects of combination and sequential therapy on tumor growth. The efficacy of AIs in the treatment of hormone receptor-positive breast cancer was first demonstrated in five multicenter second-line trials enrolling several hundreds of postmenopausal patients with metastatic breast cancer who had failed tamoxifen treatment. More recently, anastrozole demonstrated efficacy at least equivalent to that of tamoxifen in first-line randomized, phase III clinical trials in postmenopausal women with hormone receptor-positive or unknown metastatic breast cancer, whereas letrozole demonstrated superiority. The steroidal AI exemestane is currently under evaluation. Letrozole is the only AI to have been studied in a randomized, phase III trial in the neoadjuvant setting. In this trial, more patients underwent breast-conserving surgery with letrozole than with tamoxifen. Smaller phase II studies also suggest that both anastrozole and exemestane are active in the neoadjuvant setting. Because neoadjuvant trials permit temporal sampling of breast tissue, substudies in the phase III trial with letrozole have examined the impact of such biomarkers as estrogen receptor, progesterone receptor and epidermal growth factor receptor family members, HER-1 and HER-2, on patient response. AIs are currently under evaluation in the adjuvant setting, and preliminary results of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial have been reported. AIs have proven as safe as tamoxifen in trials in patients with metastatic breast cancer. Ongoing clinical trials in the adjuvant setting include companion studies of end-organ effects, particularly bone metabolism and lipid metabolism evaluations. Quality-of-life assessments are also parts of major clinical trials. A head-to-head quality-of-life assessment of anastrozole compared with letrozole demonstrated patient preference for letrozole. These assessments also clearly indicated the eagerness of patients to participate actively in treatment decisions
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PMID:Challenges in the endocrine management of breast cancer. 1465 38

This is the first report in the English literature of a composite endometrial tumor composed of papillary serous carcinoma and small cell carcinoma. A 79-year-old woman underwent total abdominal hysterectomy and left salpingo-oophorectomy due to endometrial carcinoma. Grossly, the uterus was enlarged with an irregular and nodular serosal surface, thickened myometrium, and irregular endometrium. Microscopic examination revealed an endometrial carcinoma composed of papillary serous carcinoma and small cell carcinoma. There was a differential immunoreactivity between the two components: the cells of the papillary serous carcinoma were positive for cytokeratin, CA-125, CEA, and HER-2/Neu, whereas these markers were negative in the small cell carcinoma. Various neuroendocrine markers were positive in the small cell carcinoma and negative in the papillary serous carcinoma. Fluorescence in situ hybridization analysis using 4, 8, and 10 centromeric probes revealed hyperploidy (6-8 signals) in the small cell carcinoma cells. Most of the serous carcinoma cells were euploid, with scattered trisomies and tetrasomies of these chromosomes. The patient died of progressive disease 5 months after surgery. We suggest that the small cell carcinoma may have arisen from the endometrial papillary serous carcinoma undergoing tumor progression with neuroendocrine differentiation.
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PMID:An unusual composite endometrial tumor combining papillary serous carcinoma and small cell carcinoma. 1525 20

A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.
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PMID:The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers--a study of the National Cancer Institute of Canada Clinical Trials Group. 1530 61

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.
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PMID:[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006]. 1700 57

Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).
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PMID:HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications. 1700 89

Uterine serous papillary carcinoma (USPC) is a rare and highly malignant form of endometrial cancer (EC) characterized by early metastasis, chemoresistance, and high mortality rate. Little is known about USPC tumorigenesis even if recently a HER-2/neu role has been suggested in its development and progression. The aim of the present study was to evaluate HER-2 expression by immunohistochemistry (IHC) in 12 USPC formalin-fixed, paraffin-embedded (FFPE) samples. Moreover, we looked at the correlation between HER-2 protein expression and HER-2/neu gene amplification by fluorescence in situ hybridization (FISH), other than HER-2/neu messenger RNA expression by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Finally, these results have been compared with commonly evaluated clinical features in EC patients, in order to define the potential prognostic value of HER-2/neu overexpression in USPCs. A high expression of HER-2 protein by IHC was noted in 2 of 12 patients (16.6%), and the same cases showed specific HER-2/neu gene amplification by FISH. All the samples investigated displayed a perfect concordance between IHC and FISH data. Five (41.6%) of 12 tumors demonstrated polysomy of chromosome 17 and, focusing on the 2 USPCs that showed HER-2/neu overexpression, one of them (50%) was polysomic for chromosome 17. All the other USPC cases (58.4%) showed to be disomic for chromosome 17. Quantitative RT real-time PCR performed on complementary DNA obtained from all FFPE USPC samples showed a complete correlation with FISH and IHC data. Moreover, HER-2/neu overexpression was associated with a poorer overall survival and a very low relapse-free survival time, thus being considered a candidate marker of worse overall prognosis in USPC. The use of trastuzumab (Herceptin), a monoclonal antibody directed against HER-2/neu, for the therapy of patients with HER-2/neu-positive USPCs should be further investigated in clinical trials.
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PMID:HER-2/neu overexpression and amplification in uterine serous papillary carcinoma: comparative analysis of immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization. 1745 61


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