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)

We have studied by immunocytochemistry and monoclonal antibodies the presence and localization of estrogen receptors, progesterone receptors, and a 24-kD estrogen-regulated heat shock protein in biopsies from breast and endometrial cancer patients. Three different tissue processing protocols were used to colocalize the antigens in the same tissue sections: a) frozen sections, b) formalin fixation with routine paraffin embedding, and c) picric acid-formaldehyde (PAF) fixation with a rapid embedding in paraffin. Frozen sections showed good receptor staining but poor 24-kD protein immunoreactivity, while routine paraffin sections (with or without DNase pretreatment) were inadequate to reveal the nuclear receptor proteins at the same level seen in frozen sections. On the other hand, all three proteins could be detected satisfactorily in PAF-fixed paraffin-embedded tissue. Using this procedure we were able to visualize 24-kD protein and estrogen receptor or progesterone receptor in individual cells in paraffin sections. The study revealed that in all of the estrogen receptor positive breast and endometrial tumor samples, almost 90% of the cells expressing the cytoplasmic 24-kD protein contained estrogen receptor in the cell nucleus. In contrast, 24-kD immunoreactive cells did not express progesterone receptors in almost 40% of the progesterone receptor positive tumor samples.
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PMID:Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue. 208 75

Using immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinicopathological parameters in patients with endometrial cancers. Formalin-fixed and paraffin-embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear-cell type, 1) were stained with anti-p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer. Lymph-node metastasis was also related to p53 overexpression with marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis showed p53 overexpression to be associated with a poor outcome in endometrial cancer patients. However, multivariate analysis using the stepwise Cox proportional-hazard model showed that whereas lymph-node metastasis, a personal history of cancer and muscular invasion were related to poor survival rates, p53 overexpression was not. Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively.
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PMID:Clinicopathological characteristics of p53 overexpression in endometrial cancers. 801 10

A metastatic tumor suppressor role for the nm23 gene product in breast carcinoma has been proposed. The biologic significance of nm23/NDP kinase-A (NDPK-A) expression in endometrial carcinoma remains undetermined. We sought to (1) characterize the pattern and intensity of nm23 protein expression in endometrial carcinoma and (2) assess the relationship between intensity/pattern of nm23 protein immunostaining and treatment response assessed by progression-free survival and survival to death. Formalin-fixed paraffin-embedded sections from 234 patients with endometrial cancer were immunostained with a mouse monoclonal IgG to nm23/NDPK-A protein. In most specimens of endometrial carcinoma (67.5%), nm23 expression was strongly upregulated. No association was found between either intensity (0 vs 1, 2, 3) or pattern (nuclear membrane vs cytoplasmic) of immunostaining and FIGO stage, ploidy status, histologic subtype, myometrial invasion, progression-free survival, or survival to death. Absence of nm23 staining (0 vs 1, 2, 3) was significantly associated with lower tumor grades (P = 0.02). For stage I patients, moderate to strong nm23 immunostaining intensity (2, 3) was associated with a trend toward diminished progression-free survival (P = 0.08). Our data imply a heterogeneity of nm23 protein expression and possible distinct biologic roles for nm23 in endometrial compared with breast or ovarian carcinoma.
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PMID:Expression of nm23/nucleoside diphosphate kinase-A protein in endometrial carcinoma. 926 69

Purposes of the study were to evaluate the correlation between intratumoral blood flow and stage, histologic grade, depth of myometrial invasion and lymph node metastasis in endometrial carcinoma and to assess if vascular/lymphatic spaces invasion is predictable by Doppler ultrasound. Fifty-three patients with endometrial carcinoma were enrolled before surgical treatment. Transvaginal Color Doppler Ultrasound was performed to detect the areas of increased vascularity (>/=3) and to record the lowest resistance index (RI) from the blood flow signals within the tumour. Formalin fixed, paraffin embedded pathology slides were reviewed by a senior pathologist to evaluate histologic grading, depth of myometrial invasion, presence of lymph node metastasis and vascular/lymphatic spaces invasion. The number of patients with positive lymph node metastasis was too small to perform any statistical evaluation. Significantly lower RI was noted in tumours of advanced stage (>FIGO Stage I), tumours with higher histologic grade (Grade 3) and with presence of vascular invasion. No correlation was found for myometrial invasion (>50%). A high number of vascular areas was positively correlated with all the prognostic signs. Assessment of tumour changes in vascularity using colour Doppler ultrasound provides useful information for the preoperative prediction regarding stage and histologic grade. The good correlation between Doppler ultrasound results and histological finding of vascular/lymphatic spaces invasion is another point in favour of routine colour Doppler studies in patients with endometrial carcinoma. We believe this technique is useful both for preoperative staging and that recording of tumour recurrence pattern may lead to early selection of those patients that need additional therapy.
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PMID:Intratumoral blood flow characteristics and prognostic factors in patients with endometrial carcinoma. 1241 Mar 63

Cancer-testis (CT) antigens are expressed in a variety of malignant tumors, but in normal adult tissue, they are only expressed in testicular germ cells. Owing to this tumor-associated expression pattern, these antigens are of major interest as potential targets for immunotherapy and possibly for diagnostic purposes. This study was performed to analyze the expression of four CT antigens, NY-ESO-1, MAGE-A3, MAGE-A4, and CT7/MAGE-C1, in endometrial carcinoma using immunohistochemistry, and to correlate expression with histologic subtypes, grade, and expression of WT1 and p53. Formalin-fixed paraffin-embedded tissues of 130 endometrial carcinomas of the following types and grades were analyzed using a tissue microarray: 85 endometrioid carcinomas (FIGO grade 1, 39; grade 2, 11; and grade 3, 35), 18 papillary serous carcinomas, 12 clear cell carcinomas, 13 malignant mixed mullerian tumors, one mucinous adenocarcinoma, and one undifferentiated carcinoma. The following anti-CT monoclonal antibodies/antigens were studied by immunohistochemistry: monoclonal antibody ES121/NY-ESO-1, monoclonal antibody M3H67/MAGE-A3, monoclonal antibody 57B/MAGE-A4, and monoclonal antibody CT7-33/CT7. The CT expression data were compared to WT1 and p53 protein expression as analyzed in a previous study. Positive staining with anti-CT monoclonal antibodies was graded as follows: focal, <5% positive cells; 1+, 5-25% cells; 2+, 26-50% cells; 3+, 51-75%; and 4+, >75% cells. The 3+ and 4+ staining patterns were considered homogeneous patterns of potential clinical significance and were scored positive for statistical analysis. In low-grade tumors, the most immunoreactivity was seen with mAb M3H67 but little labeling was observed with the other monoclonal antibodies. In high-grade tumors, monoclonal antibodies M3H67 (25%), 57B (23%), and CT7-33 (20%) showed the highest reactivity, while ES121 showed the lowest immunoreactivity (6%). The staining pattern was mostly heterogeneous. Statistical significance was found solely for the correlation of monoclonal antibody 57B staining and p53 expression. No correlation was found for any anti-CT monoclonal antibody staining and clinical stage or for anti-CT staining and WT1 expression. CT antigens CT7, MAGE-A3 and MAGE-A4, but not NY-ESO-1, are expressed in high-grade endometrial carcinomas, and expression of MAGE-A4 is correlated with the presence of overexpressed p53.
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PMID:Expression of cancer-testis antigens in endometrial carcinomas using a tissue microarray. 1527 78

Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.
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PMID:Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions. 1700 91

The aim of this study was to compare vascular endothelial growth factor (VEGF), CD 34, and endoglin expressions as markers of angiogenesis in proliferative endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC) and to find the possible impact of angiogenesis on malign transformation. Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients with simple EH and complex EH with atypia, and 31 patients with EC were included. A semiquantitative scoring system was used to assess the intensity and degree of staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti-CD 34 in most vascular areas. VEGF expression was significantly higher in EC and EH than PE, but there was no difference between EC and EH. According to CD 34 staining, there were no differences in MVD between groups. However, mean MVD counts assessed by endoglin were significantly higher in EC than PE and EH. Although VEGF expression in EC was significantly higher, it did not correlate with other measures of angiogenesis. MVD using endoglin seemed to reflect neoplastic angiogenesis better than CD 34.
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PMID:Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma. 1744 20

Ret finger protein (RFP) is a nuclear protein with transcriptional repressive activity that is highly expressed in a variety of human and rodent tumor cell lines. We examined the expression of RFP in human endometrial cancer and assessed its clinical significance. Formalin-fixed, paraffin-embedded sections from endometrial cancer tissues were immunostained with the RFP antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics stage, tumor grade, myometrial invasion, and pelvic lymph node metastasis. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 119 cancer tissues, 57 (47.9%) cases were positive for RFP immunoreactivity. RFP expression was not associated with any of the clinicopathological parameters examined. However, positive RFP expression significantly predicted poorer OS and PFS compared with negative expression (OS, P = 0.0011; PFS, P < 0.0001). In the multivariate analyses, positive RFP expression was an independent prognostic factor for survival in this study. RFP knockdown significantly impaired cancer cell migration and invasion in vitro with concomitant decreases of integrins beta1 and alpha2. Positive RFP expression is a predictive marker for an unfavorable clinical outcome in patients with endometrial cancer.
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PMID:Expression of Ret finger protein correlates with outcomes in endometrial cancer. 1965 Aug 60

Formalin-fixed paraffin-embedded (FFPE) tissues are the primary and preferred medium for archiving patients' samples. Here we demonstrate relative quantifications of protein biomarkers in extracts of laser microdissected epithelial cells from FFPE endometrial carcinoma tissues versus those from normal proliferative endometria by means of targeted proteomic analyses using LC-multiple reaction monitoring (MRM) MS with MRM Tags for Relative and Absolute Quantitation (mTRAQ) labeling. Comparable results of differential expressions for pyruvate kinase isoform M2 (PK-M2) and polymeric Ig receptor were observed between analyses on laser microdissected epithelial cells from FFPE tissues and corresponding homogenates from frozen tissues of the same individuals that had previously been analyzed and reported. We also identified PK-M2 in the normal proliferative phase of the endometrium. Other biomarkers in addition to PK-M2 and polymeric Ig receptor were also observed but not consistently and/or were at levels below the threshold for quantification.
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PMID:mTRAQ-based quantification of potential endometrial carcinoma biomarkers from archived formalin-fixed paraffin-embedded tissues. 2066 55

Thyroid transcription factor-1 (TTF-1) is a DNA-binding protein that is mainly expressed in thyroid and lung tissue, but has also been found in gynecologic tissue. Recent studies have suggested that TTF-1 has tumor suppressor function in lung adenocarcinoma models. In the current study, we examined whether expression of TTF-1 in benign endometrium and endometrial hyperplasia might impact on the risk of developing endometrial cancer. Formalin-fixed paraffin-embedded endometrial tissues obtained from 535 cases were used to construct an endometrial tissue microarray. One hundred fifty of 207 patients had multiple serial endometrial specimens including 46 patients who progressed to endometrial cancer. The tissue microarray included a range of histopathologies including benign endometrium (n=231), simple hyperplasia (n=105), complex hyperplasia (n=36), simple atypical hyperplasia (n=10), complex atypical hyperplasia (n=44), and endometrial carcinoma (n=109). Expression of TTF-1 by immunohistochemistry in benign endometrium and endometrial hyperplasia was correlated with progression to cancer and clinical features known to be associated with increased risk of developing endometrial cancer. Carcinoma specimens showed a significantly greater expression of TTF-1 compared with benign endometrium and non-atypical hyperplasia (P=0.0007 and P=0.05). Presence of TTF-1 expression in benign endometrium was associated with a significantly decreased risk of cancer development (P=0.003, hazards ratio=0.104, 95% CI: 0.024-0.455). TTF-1 expression in hyperplasia did not significantly correlate with progression to cancer. The data from our study show that TTF-1 expression in normal endometrium is associated with a reduced risk of endometrial cancer development. This observation suggests that TTF-1 might function as a tumor suppressor in endometrial tissue. TTF-1 expression in normal endometrium could potentially provide clinically useful information as a biomarker for the risk of endometrial cancer.
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PMID:Expression of thyroid transcription factor-1 in normal endometrium is associated with risk of endometrial cancer development. 2246 Aug 11


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