Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E-cadherin/catenin complex plays a major role in epithelial cell-cell adhesion. Both beta-catenin and gamma-catenin bind directly to the cytoplasmic domain of E-cadherin whereas alpha-catenin links the bound beta-catenin or gamma-catenin to the actin microfilament network of the cellular cytoskeleton. Significant changes in the expression and/or structure of members of the complex can occur in neoplasia. Several studies have reported on the nuclear localization of beta- and gamma-catenin and on their role in influencing the transcriptional activity of several proto-oncogenes. The cellular localization of alpha-catenin has not been studied in detail. The aim of this study was to investigate the cellular localization of alpha-catenin in colorectal carcinoma both in vitro and in vivo and to assess whether it might be relevant to tumor behavior. The expression of alpha-catenin was examined in a panel of colorectal carcinoma cell lines (SW480, SW620, HCT116, HT29, and Caco-2) using a combination of immunohistochemistry, confocal fluorescence microscopy, and Western blotting. The expression of alpha-catenin was also studied by immunohistochemistry in 15 sporadic colorectal adenomas, 30 sporadic colorectal adenocarcinomas, and their 13 lymph node metastases. From familial adenomatous polyposis patients, 20 adenomas and 5 adenocarcinomas were studied. Nuclear localization of alpha-catenin was detected in the colorectal carcinoma cell lines when the cells were dispersed rather than confluent. alpha-catenin was not detected in the nuclei in any of the sporadic or familial adenomas. However, it was detected in one sporadic and one familial adenocarcinoma but not in any of the lymph node deposits. alpha-catenin can localize to the nuclei of colorectal tumor cells, and this may be related to lack of perception of connection to adjacent cells.
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PMID:Variable nuclear localization of alpha-catenin in colorectal carcinoma. 1221 77

Wilms' tumour is a pediatric neoplasm exhibiting histologic features of developing kidney. Although the majority of Wilms' tumour patients are treated effectively, approximately 15% develop metastases and of these, 30% succumb to their disease. The biologic factors governing Wilms' tumour metastasis are largely unknown. Attempts at deriving representative Wilms' tumour cell lines, which could facilitate functional studies, have only been partially successful thus far. We now report on derivation and characterization of a Wilms' tumour cell line, WiT 49, from a first-generation xenograft of a human Wilms' tumour lung metastasis. WiT 49 recapitulates the phenotype of the parent tumours (primary and lung metastasis) and expresses normal WT1, overexpresses IGFII and carries a frequently identified p53 mutation. We recently reported overexpression of hepatocyte growth factor(HGF) and its receptor met in a series of Wilms' tumours with higher levels in homotypic metastatic cases. We therefore examined WiT 49 for expression of HGF/met and for met signaling targets associated with cell adhesion and cytoplasmic mediators of transcription using Western blot, co-immunoprecipitation, immunofluorescence labeling and zymography. Our results show co-expression of HGF and met protein, absence of E-cadherin, high levels of beta-catenin co-immunolocalized to met at the cell membrane and moderate levels of gamma-catenin and ezrin protein expression. After cell fractionation, beta-catenin was detected in the cytoplasm and nuclei of WiT 49 with relatively higher levels in the cytoplasm as compared to nuclei. Examination of MMP expression in WiT 49 showed constitutive activation of MMP 9 and latent MMP 2 supporting possible beta-catenin-mediated transcriptional activation. The WiT 49 cell line responded to recombinant human HGF by an increase in the expression of the met receptor, recruitment of the Gab-1 adapter protein to met and release of bound beta-catenin from met. Our studies therefore establish WiT 49 as a representative Wilms' tumour cell line derived from a lung metastasis that co-expresses HGF/met and shows absence of the cadherin-catenin complex supporting a role for these factors in regulation of the invasive and metastatic phenotype in Wilms' tumour.
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PMID:Derivation and characterization of a Wilms' tumour cell line, WiT 49. 1450 35

Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key participants in the Wnt cell signalling pathway, in which aberrancies have been associated with malignant cell transformation. We assessed the independent prognostic value of these proteins in a clinical material. Tumours from a series of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas were analysed using semiquantitative immunohistochemistry and the results were related to patient outcome. Patients expressing nuclear beta-catenin in the primary tumour showed reduced survival compared to other patients (log rank p=0.028) and there was also an association with development of metastases follow-up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co-expression of nuclear beta-catenin and c-Myc turned out to be the strongest marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have independent prognostic significance in our study.
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PMID:Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas. 1496 75

Epithelial cadherin forms a complex with alpha-, beta-, and gamma-catenin proteins. Reduced expression of E-cadherin-catenins has been shown in human carcinomas and is associated with low histologic differentiation, increased risk of invasion, and metastatic disease. The immunoexpression pattern of E-cadherin and beta-catenin (reduced versus preserved phenotype) was evaluated in 104 primary ovarian carcinomas and related to clinicopathologic features of the tumors. The immunoexpression pattern of E-cadherin was associated with International Federation of Gynaecology and Obstetrics (FIGO) staging (P = 0.043), histologic subtype (P = 0.001), peritoneal metastasis (P = 0.006), and residual tumor (P = 0.036). The reduced phenotype of E-cadherin that was observed in 64% of the carcinomas (67/104) was associated with advanced stage tumors, serous carcinomas, presence of peritoneal metastasis, and residual tumor larger than 2 cm. The immunoexpression pattern of beta-catenin was associated with histologic subtype (P = 0.005), tumor differentiation (P = 0.025), and peritoneal metastasis (P = 0.041). The reduced phenotype of beta-catenin that was observed in 74% of the carcinomas (77/104) was associated with advanced stage tumors, poorly differentiated serous and clear cell carcinomas, presence of peritoneal metastasis, and residual tumor. The immunoexpression pattern of E-cadherin was correlated with beta-catenin (P = 0.001). The reduced phenotype for both E-cadherin and beta-catenin was associated with histologic subtype (P < 0.001) and peritoneal metastasis (P = 0.001). In conclusion, the immunohistochemical profile of E-cadherin and beta-catenin may be useful in identifying a particular subpopulation of ovarian cancer patients who are characterized by an adverse clinical outcome, because the reduced phenotype of these molecules was associated with poor tumor differentiation, peritoneal metastasis, and advanced FIGO stage tumors.
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PMID:Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. 1518 29

The catenins (alpha-, beta- and gamma-) are cytoplasmic proteins that bind to the conserved tail of the epithelial cadherin molecule. The function of epithelial cadherin at the adherens junctions is dependent on the catenins for efficient cell-to-cell adhesion. Loss of catenin expression has been reported in several human cancers and associated with poor tumor differentiation, advanced tumor stage, and poor patient survival. In this study, we investigated the clinical relevance of alpha-, beta-, and gamma-catenin immunoexpression in 104 cases of primary ovarian carcinoma with respect to clinicopathological features and as predictors of disease recurrence and prognosis. The clinicopathological parameters studied were International Federation of Gynaecology and Obstetrics (FIGO) stage, histological type, tumor differentiation, peritoneal metastases, residual postoperative tumor, integrity of the tumor's serosal surface, peritoneal cytology, and lymphatic/vascular invasion. Negative immunoreactivity of alpha-catenin, beta-catenin, and gamma-catenin was observed in 22 (21%), 15 (14%) and 23 (22%) cases, respectively. Immunoreactivity of alpha-catenin and gamma-catenin did not correlate with any of the clinicopathological parameters tested. The immunoexpression pattern of beta-catenin correlated with histological type (p = 0.026) and with a poorer overall survival in univariate analyses (p = 0.022). In the group of serous carcinomas, beta-catenin-immunoexpression associated significantly with overall survival. Patients with beta-catenin-negative serous carcinomas had a poorer overall survival than patients with beta-catenin-positive serous carcinomas (p = 0.013). In the multivariate analysis, negative expression of beta-catenin (p = 0.003) and the presence of residual tumor (p = 0.019) were the two most important independent prognostic factors predicting poorer overall survival. In conclusion, negative immunoreactivity of beta-catenin in serous carcinomas and the presence of residual tumor seem to be useful markers in selecting patients likely to have an unfavorable course.
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PMID:Loss of beta-catenin is associated with poor survival in ovarian carcinomas. 1538 3

The case of a 46-year-old female with umbilical metastasis as a first sign of an ovarian carcinoma is reported with the results of immunohistochemical analysis of primary tumor and lymph node and umbilical metastases. All specimens were positive for cytokeratin 7, CA 125, E-cadherin, alpha-, beta-, and gamma-catenin, as well as for MSH2. Staining with cytokeratin 20 and MLH1 was negative, and Ki-67 labeled from 5% (in the center of the lesions) to over 25% (at the periphery of the lesions) of the nuclei. Beta-catenin showed membranous positivity in the central parts and absence of staining at the periphery of ovarian tumor and umbilical metastasis, whereas lymph node metastasis presented with uniform reaction throughout. The results of immunohistochemical staining could point to the mechanisms employed by malignant tumors during invasion and growth of metastasis and suggest the possible role of the microenvironment in the expression of some adhesion molecules on tumor cells.
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PMID:Umbilical metastasis (Sister Joseph's nodule) as a first sign of a disseminated ovarian carcinoma: comparative immunohistochemical analysis of primary tumor and its metastases. 1582 29

Reduction of the expression of catenin is a crucial step in the pathogenesis, progression and prognosis of many epithelial cancers including squamous cell carcinomas (SCCs). Catenin expression in oral carcinomas was evaluated in relation to clinico-pathological features in order to determine its value as a prognostic marker. Eighty-five patients with histologically proven T1/2 squamous cell carcinoma of the oral floor who underwent surgical treatment were eligible for the study. A tissue microarray consisting of multiple representative tissue cores of each carcinoma was composed. The expression levels of alpha, beta and gamma-catenins were determined immunohistologically. Correlation between clinical features and the expression of catenin proteins was evaluated statistically using Kaplan-Meier curves, log-rank tests and chi(2)-tests. Loss of alpha-catenin expression in carcinoma of the floor of the mouth correlated significantly with poor prognosis (P=0.05). Conversely, significantly reduced rates of lymph-node metastases were observed in alpha- and beta-catenin-positive T1 and T2 SCCs. Loss of gamma-catenin expression indicated a reduced survival rate in nodal-negative tumours (P=0.02). Catenin expression in carcinomas of the floor of the mouth seems to be a predictive parameter in the prognosis of T1 and T2 SSCs.
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PMID:Catenin expression in T1/2 carcinomas of the floor of the mouth. 1591 80

The vast majority of invasive breast tumors are ductal and lobular breast carcinomas. Despite the many similarities, some clinical follow-up data and the patterns of metastases suggest that these histological subtypes of breast cancer are biologically distinct. Few papers, however, describe immunohistochemical markers useful for differentiation of these carcinomas. Many investigations suggest that E cadherin protein expression is lost in lobular but not in ductal carcinoma. The absence of E-CD, as a partial loss of epithelial differentiation, may account for the extended spread of lobular carcinoma in situ and the peculiar diffuse invasion mode of invasive lobular carcinoma. Some investigations report the significance of E-CD associated proteins alpha-, beta-, gamma-catenin expression, as well as the usefulness of cytokeratins 5, 6, 8, 7 and thrombospondin in differentiating histological types of breast invasive carcinomas. Several reports have suggested the possibility that invasive ductal and lobular cancers differ with respect to expression of antigens involved in proliferation and cell cycle regulation. It has been shown that vascular endothelial growth factor expression, also the expression of maspin, a tumour suppressor gene product, is higher in ductal, than in lobular carcinoma. Expression of NKX3.1, a member of the NK-class of homeodomain, is highly restricted and is found primarily in lobular carcinoma. Some histological and immunohistochemical characteristics of pleomorphic lobular carcinoma are also discussed.
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PMID:Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas. 1617 Mar 89

Tubulolobular carcinoma is a type of mammary carcinoma that displays an admixture of invasive tubules and lobular-like cells. Previous reports have shown it to share clinical similarities to lobular carcinoma, whereas more recent studies have shown it to be E-cadherin positive. The aim of the current study was to further explore the immunophenotype of tubulolobular carcinoma, and to document its natural behavior. Nineteen cases of tubulolobular carcinoma and 10 cases each of tubular and lobular carcinoma were retrieved for comparison analysis. Immunohistochemistry was performed with antibodies against estrogen receptor, progesterone receptor, HER2/neu, 34betaE12, E-cadherin, and the catenins. Twenty-five percent of patients with tubulolobular carcinoma presented with greater than stage I disease, compared to 0 and 60% of patients with tubular and lobular carcinoma, respectively. Two patients with tubulolobular carcinoma had tumor recurrence, one of whom also developed metastasis. The majority of all carcinomas were estrogen and progesterone receptor positive. E-cadherin displayed membranous staining in all tubular and tubulolobular carcinomas, and was negative in all lobular carcinomas. Half of each carcinoma subtype displayed granular cytoplasmic 34betaE12 immunoreactivity. alpha-Catenin exhibited partial or complete membranous staining in all tubulolobular and tubular carcinomas, and was negative in all lobular carcinomas. beta-Catenin displayed membranous staining in tubulolobular and tubular carcinomas, whereas all lobular carcinomas had coarse cytoplasmic immunoreactivity. p120 and gamma-catenin displayed membranous staining in 100% of tubulolobular and tubular carcinomas and cytoplasmic staining in 100% of lobular carcinomas. Tubulolobular carcinoma of the breast is thus a distinct type of mammary carcinoma that displays both tubular and lobular patterns histologically but displays the membranous E-cadherin/catenin complex characteristic of the ductal immunophenotype. Tubulolobular carcinoma appears to be more aggressive than tubular carcinoma, as 16% of patients had lymph node metastases, although all were alive at a mean follow-up of 40 months.
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PMID:The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study. 1865 93

Reduced intercellular adhesion is implicated in the development of metastasis. This study investigates the expression of intercellular adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7) and their influence on survival in primary breast carcinomas and corresponding axillary lymph node metastases (ALNM), and evaluates associations between them and with clinicopathological factors. The expression of adhesion molecules was analyzed immunohistochemically in tissues from 196 patients with primary invasive breast carcinomas and their nodal metastases (174 ductal and 22 lobular types). The expression was evaluated using semi-quantitative scoring of the intensity and proportion of immunoreactivity. All five adhesion proteins showed significantly reduced expression in primary ductal carcinomas with re-expression in ALNM (p<0.001). In uni- and multivariate analyses, the expression of E-cadherin in the primary tumours was a significant predictor of disease-free survival and distant disease-free survival. Thus, abnormal E-cadherin expression in the primary invasive breast carcinoma seems to be an independent prognostic biomarker in predicting a shorter survival in node-positive breast cancer patients. The results indicate that abnormal expression of the adhesion molecules in the primary tumours with re-expression in corresponding nodal metastases is a common event in breast ductal carcinomas and may play a central role in establishing metastasis.
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PMID:Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. 1722 51


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