UMLS:C0476089 - FACTA Search

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

p63 and cytokeratin (CK) 5/6 are markers of basal and squamous differentiation in several normal epithelia and human tumors and are also suggested to be markers of progenitor or stem cells in certain stratified epithelia. In endometrial carcinoma, there is very limited information about the expression pattern of p63 or CK5/6 and no prognostic information. The aim of our study was to examine whether the expression of these markers was associated with a certain tumor phenotype in terms of other biomarkers, clinicopathologic characteristics and patient prognosis. Immunohistochemical expression of p63 and CK5/6 was examined using tissue microarrays (TMAs) in a large population-based series of 276 endometrial carcinomas with long and complete follow-up. Selected cases of normal and hyperplastic endometrium were examined for comparison (n = 15). Absence of p63 expression (70%) was significantly associated with nonendometrioid carcinomas, high histologic grade (FIGO), higher mitotic count and tumor cell proliferation by Ki-67, microsatellite instability (MSI) and loss of hMSH6 expression. A tendency toward reduced patient survival was also seen (p = 0.098). Presence of CK5/6 expression was more frequent in endometrioid tumors with squamous differentiation, while loss of CK5/6 expression (54%) was significantly associated with high FIGO stage, reduced beta-catenin expression, MSI and reduced patient survival (p = 0.0001); the latter was also found within the endometrioid subgroup (p = 0.0004). Multivariate survival analysis revealed that loss of CK5/6 expression had an independent prognostic impact in addition to well-known prognostic variables. Expression of both markers was increased in simple hyperplasia compared with normal endometrium. In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only. Thus, loss of p63 or CK5/6 was associated with features of aggressive tumors, and lack of CK5/6 was significantly associated with reduced survival in multivariate analysis.
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PMID:Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients. 1615 5

PTEN is involved in the regulation of normal cellular functions in addition to its well-known role as a tumor suppressor. In the present study, we have shown that stable transfection of the PTEN gene into PTEN-mutated endometrial carcinoma cells leads to contact inhibition accompanied by a decreased level of phosphorylated-Akt (p-Akt) expression, an increase in p27(Kip1), and a decrease in beta-catenin. PTEN-induced cells with contact inhibition exhibit G0-G1 cell-cycle arrest, and the Ki-67 labeling index is reduced. These changes are canceled by transfection of a double-stranded short-interfering RNA against the PTEN gene. Normal endometrial stromal cells increase their PTEN expression when reaching confluence; this is followed by changes in the expression of Akt-related proteins in the same way as in tumor cells. These results indicate that PTEN, p-Akt, p27, and beta-catenin are involved in the signal transduction of contact inhibition and suggest that PTEN may, in part, control the proliferation of endometrial carcinoma cells through the induction of contact inhibition.
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PMID:PTEN is involved in the signal transduction pathway of contact inhibition in endometrial cells. 1628 92

Multicentric reticulohistiocytosis (MRH) is a rare histocytic disease characterized by destructive arthritis in association with classic skin findings. Although MRH is not strictly a paraneoplastic disease, one quarter of cases are malignancy related. We report a case of MRH with an initial remission followed by an acute exacerbation several years later heralding the clinical presentation of endometrial carcinoma. During this flareup a skin biopsy specimen revealed a diffuse dermal infiltrate composed of histiocytes with ground-glass cytoplasm and multiple atypical mitoses. Approximately 40% of the cells stained with the proliferation marker Ki-67. Treatment of endometrial carcinoma resulted in improvement of skin and joint symptoms, and a repeat biopsy specimen no longer demonstrated mitotic figures. These findings support a reactive and proliferative cause of MRH.
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PMID:Proliferating multicentric reticulohistiocytosis associated with papillary serous carcinoma of the endometrium. 1631 73

Angiogenesis is essential for tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/factor VIII staining) and the degree of pericyte coverage [by alpha-smooth muscle actin (alpha-SMA)/factor VIII staining], in a large and population-based series of endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D and basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the alpha-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of endometrial carcinoma.
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PMID:Vascular proliferation is important for clinical progress of endometrial cancer. 1654 Jun 84

The purpose of this study was to evaluate the prognostic significance of steroid hormone receptor proliferation index in endometrial adenocarcinoma. In this study, the correlation between oestrogen receptor expression, proliferation index and FIGO grade, age, myometrial invasion, tumour size and menopause status was evaluated in 40 patients with endometrial carcinoma. For this purpose, all tumours were stained immunohistochemically with oestrogen receptor and Ki-67 monoclonal antibodies. Oestrogen receptor expression and proliferation indices were found to be statistically associated with grade, age, menopausal status, vascular invasion and tumour size ( p < 0.001). Quantitative assessment of tumour proliferation and expression of oestrogen receptor were found to be important prognostic indicators in endometrial adenocarcinoma.
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PMID:The prognostic importance of proliferative activity and oestrogen receptor expression in stage I endometrial carcinomas. 1713 35

Gene alterations and overexpression of various oncogenes and cell-cycle regulators are important in tumor development. In a population based series of 316 endometrial carcinomas with long and complete follow-up we investigated the distribution of HER-2/neu and EGFR expression and copy number alteration in endometrial cancers. HER-2/ neu, EGFR and Ki-67 expression in curettage and hysterectomy specimens were studied immunohistochemically for expression in relation to molecular markers and clinical phenotype. Fresh tumor samples (n=76) were studied by global characterization of genetic alterations by single nucleotide polymorphism (SNP) array for detection of high level amplification for HER-2/neu and EGFR. Pathological expression of HER-2/neu in curettage was detected in 23% which significantly correlated to high FIGO stage, non-endometrioid subtype, high grade and aneuploidy. In hysterectomy specimens, pathological HER-2/neu staining was seen in 13% which correlated significantly with high FIGO stage, non-endometrioid subtype, high proliferation and poor survival (p=0.009). Expression of EGFR was examined with three different antibodies, but none showed significant correlation with molecular markers or clinical phenotype. High level amplification of HER-2/neu or EGFR was seen in only one out of 76 samples, respectively. High proliferation estimated in tumors from hysterectomy specimens showed independent prognostic impact and was superior to estimation in curettage specimens as a prognostic marker. In conclusion, high level amplification of HER-2/neu or EGFR is infrequent in endometrial cancer. Pathological HER-2/neu staining identifies endometrial carcinomas with an aggressive phenotype, high proliferation and patients with poor survival in a population based setting. These results motivate further clinical trials with trastuzumab based on HER-2/neu status in endometrial carcinomas.
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PMID:HER-2/neu expression is associated with high tumor cell proliferation and aggressive phenotype in a population based patient series of endometrial carcinomas. 1820 52

We have previously reported on vasohibin as a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible inhibitor of angiogenesis. The aim of our present study was to define the role of vasohibin in endometrioid endometrial adenocarcinoma. We collected 78 sections of endometrial carcinoma for assessment using immunohistochemistry. Twenty-seven were well differentiated (G1), 25 were moderately differentiated (G2), and 26 were poorly differentiated endometrioid adenocarcinomas (G3). We also included 12 sections of normal cyclic endometria, six of which were in the proliferative phase and six were in the secretory phase. We investigated the expression of vasohibin, and compared it to VEGF receptor-2 (VEGFR-2: KDR/flk-1), CD34, Ki-67, VEGF-A, and D2-40 (as a lymphatic vessel marker). We assessed the ratio of vasohibin- and VEGFR-2-positive vessels in the stroma of endometrial carcinoma. Immunohistochemical assessment was classified as negative or positive based on staining intensity. Vasohibin was selectively expressed on vascular endothelial cells in both cyclic endometria and endometrial carcinomas. Vasohibin was highly expressed in the normal functional endmetrium of the secretory phase, especially in the spiral artery, and was highly expressed in all grades of endometrioid adenocarcinomas. The stromal endothelial cells in G3 expressed vasohibin and VEGFR-2 more frequently than these in G1. In endometrioid adenocarcinomas, there was a significant correlation between the expression percentage of vasohibin and that of VEGFR-2 (P < 0.0001, r(2) = 0.591). This is the first study to elucidate the correlation between expression of vasohibin in the stromal endothelial cells and that of VEGFR-2 in human carcinomas.
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PMID:Expression of vasohibin as a novel endothelium-derived angiogenesis inhibitor in endometrial cancer. 1832 46

Mucinous and microglandular adenocarcinomas of the endometrium (MUC-AD and MIGL-AD, respectively) are uncommon types of endometrial cancer. When present in endometrial biopsy or curettage, these tumors may display a unique microglandular architectural pattern mimicking benign microglandular hyperplasia (MGH) of the endocervix. We compared the immunoprofile of MUC-AD and MIGL-AD with that of MGH and benign endocervical glands to identify the markers that would reliably separate these malignancies from benign endocervical tissue. A total of 10 MIGL-AD and 30 MUC-AD cases were collected for the study. Fifteen consecutive cases of benign endocervical glands and MGH were used as a control group. All cases were stained for vimentin, p16, Ki-67, BCL-2, survivin, CD10, and CD34. p16 was the only marker that showed a significantly different staining pattern between the benign and malignant cases, whereas the staining for vimentin, Ki-67, BCL-2, and survivin demonstrated marked overlaps. All but 1 MUC-AD and MIGL-AD cases were positive for p16, whereas none of the cases of benign mucinous endocervical epithelium and MGH showed p16 positivity. Furthermore, the stromal cells of endocervix demonstrated weak to moderate positivity for CD10 and strong positivity for CD34, whereas endometrial tumors showed a reverse pattern, with strong stromal positivity for CD10 and either no, or only weak, staining for CD34. In conclusion, epithelial p16 and stromal CD10/CD34 immunostaining can be useful in distinguishing MUC-AD and MIGL-AD from benign endocervical epithelium in endometrial sampling.
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PMID:Immunohistochemical differences between mucinous and microglandular adenocarcinomas of the endometrium and benign endocervical epithelium. 2056 57

Eosinophilic syncytial change (ESC), also known as papillary syncytial change, occurs in association with endometrial breakdown and bleeding, especially in nonphysiological conditions. When prominent, this morphological alteration yields a pattern of eosinophilic epithelial cells, often in pseudopapillary arrangements that can mimic cellular changes seen in metaplastic and atypical endometrium. To determine if ESC represents a proliferative, regenerative process or a degenerative, retrogressive alteration, we assessed whether the cells of ESC were actively growing. Our methodology involved a retrospective immunohistochemical study on endometrial biopsies with proliferation markers Ki-67 (MIB-1 antibody) and phosphohistone H3 Ser 28 (pHH3) in 15 cases of multifocal ESC associated with benign endometrium, 5 cases of atypical hyperplasia, and 7 cases of endometrial carcinoma. The Ki-67 proliferative index and the pHH3 mitotic index were calculated per 100 cells for each case. On immunohistochemical analysis, the Ki-67 labeling index was 1.3% for cases of ESC (mean age, 53 yr), 15.8% in atypical hyperplasia (mean age, 51.6 yr), and 42.6% in endometrial carcinoma (mean age, 68.1 yr). In the endometrial cancers, the Ki-67 proliferative index was 10.6% for FIGO grade 1 tumors (n=3), 27.6% for grade 2 tumor (n=1), and 79.6% for serous carcinoma (n=3). The mitotic index calculated from pHH3 immunostaining was zero in all cases of ESC, whereas it was 2.3% in atypical hyperplasia and 4.8% in endometrial carcinomas (2.4% for grade 1, 3% for grade 2, and 7.8% for serous). Our results indicate that ESC is a regressive change. Furthermore, when there is a question of whether eosinophilic endometrial epithelium represents this change, a combination of Ki-67 and pHH3 immunostains can be helpful in distinguishing this entity from more significant processes including carcinoma.
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PMID:Endometrial eosinophilic syncytial change related to breakdown: immunohistochemical evidence suggests a regressive process. 1875 67

Protein kinase CK2 (CK2) is a serine/threonine kinase that participates in important cellular processes. We have recently demonstrated that CK2 plays a role in resistance to TRAIL/Fas-induced apoptosis in endometrial carcinoma (EC) by regulating FLIP. Here, we assessed the immunohistochemical expression of CK2beta in EC and checked its role in cell proliferation and anchorage-independent cell growth. CK2beta immunostaining was assessed in two tissue microarrays, one constructed from paraffin-embedded blocks of 95 ECs and another from 70 samples of normal endometrium. CK2beta expression was correlated with histological type; grade and stage; cell proliferation (Ki-67) and apoptotic index; immunostaining for cyclin D1, PTEN, AKT, beta-catenin, and FLIP. Moreover, the Ishikawa EC cell line was subjected to down-regulation of CK2 by shRNA. CK2beta expression was frequent in EC (nuclear, 100%; cytoplasmic, 87.5%). The staining was more intense in EC than in normal endometrium (P = 0.000), and statistically correlated with AKT, PTEN, beta-catenin, and FLIP. In EC, CK2beta expression correlated with cell proliferation. Knock-down of CK2beta blocked colony formation of EC in soft agar, and also resulted in decreased expression of cyclin D1 and ERK phosphorylation. The results confirm that CK2beta is widely expressed in EC, and suggest a role in cell proliferation and anchorage-independent cell growth.
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PMID:CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation. 1905 46

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