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)

Accumulating evidences indicate that p120 catenin, a member of the E-cadherin (E-CD)/catenin adhesion complex, plays a role in tumor invasion. To establish the expression pattern of p120 in breast cancer, we analysed 326 breast tissue biopsies by tissue microarray. Most of the lobular tumors (88%) showed exclusive cytoplasmic localization, and 6% of them also had p120 nuclear staining. Cytoplasmic p120 strongly associated with complete loss of E-CD and beta-catenin not only in lobular carcinoma and its metastases but also in atypical lobular hyperplasias. In the latter, loss of heterozygosity of E-CD gene was also observed. Complete loss of E-CD and cytoplasmic and nuclear p120 staining was also observed in primary lobular cancer cell cultures generated by us. In ductal tumors, by contrast, reduction of p120 and E-CD in membrane was very common (57 and 53%, respectively), whereas cytoplasmic p120 staining was rarely seen. This simultaneous reduction of membranous E-CD and p120 was not associated with increased Src kinase activity. To demonstrate that cytoplasmic p120 localization was a consequence of the absence of E-CD, the endogenous E-CD was re-expressed in MDA-231 cells by 5-Aza-2'-deoxycytidine (5Aza) treatment. After treatment, p120 shifted from the cytoplasm to the membrane, where it colocalized with endogenous E-CD. Additionally, suppressing E-CD expression in Madin-Darby canine kidney cells by stable transfection of the transcriptional repressors Snail, E47 or Slug, provokes p120 cytoplasmic localization and p120 isoform switching. In conclusion, abnormal cytoplasmic and nuclear localization of p120, which are mediated by the absence of E-CD, characteristically occur in the early stages of lobular breast cancer and are maintained during tumor progression to metastasis. Consequently, p120 may be an important mediator of the oncogenic effects derived from E-CD inactivation, including enhanced motility and invasion, in lobular breast cancer.
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PMID:Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. 1507 90

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

Female adnexal tumor of probable Wolffian origin (FATWO) is a rare entity which is believed to originate from mesonephric (Wolffian) remnants on the basis of its location where the remnants are abundant. Its behavior is usually indolent, although some cases can recur or metastasize. The authors present the clinicopathological features of two cases of FATWO arising in the broad ligament, and focus on the expression of adhesion molecules and proliferative marker. Mesonephric duct remnants are also examined in an attempt to elucidate the histogenesis of FATWOs. The two FATWOs were well-circumscribed solid masses arising in the leaves of the broad ligament and histological examination revealed a mixture of cysts and tubules imparting a sieve-like pattern and mucin-negative eosinophilic secretion within these tubules. Immunohistochemically, the tumors showed the expression of cytokeratin 7 and 20, high-molecular-weight cytokeratin, and calretinin, which closely resembled that of the mesonephric duct remnants. Regarding CK 20, CD 10, EMA, S-100 protein, and vimentin their expression was in part not identical with previous studies. E-cadherin, alpha and beta-catenin were strongly expressed along the cell membrane of the tumor cells. The Ki-67 labeling index of FATWO was 0% and 3.2% in each case. The preservation of the E-cadherin-catenin complex and low Ki-67 labeling index could explain the indolent behavior and low malignant potential of this tumor.
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PMID:Expression of adhesion molecules and Ki-67 in female adnexal tumor of probable Wolffian origin (FATWO): report of two cases and review of the literature. 1551 Dec 77

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

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E-cadherin-mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E-cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non-micropapillary, area. The adhesive function of E-cadherin depends on the integrity of the entire cadherin-catenin-actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.
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PMID:Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern. 1598 17

Wnt signaling is a complex process that requires the interplay of several different proteins. In addition to a large cohort of Wnt ligands, and frizzled receptors, some Wnt pathways also require the presence of co-receptors. Wnt ligands may activate one of three pathways, the canonical pathway, involving beta -catenin, the planar cell polarity pathway and the Wnt/ calcium pathway. All three pathways have different results for the cells in which they signal. Aberrant activation of these pathways can lead to the development and progression of several cancers. In this review we will discuss the different Wnt pathways, and their contribution to melanoma progression.
Cancer Metastasis Rev 2005 Jun
PMID:A Wnt-er wonderland--the complexity of Wnt signaling in melanoma. 1598 34

The proteins SKI and SnoN are implicated in processes as diverse as differentiation, transformation and tumor progression. Until recently, SKI was solely viewed as a nuclear protein with a principal function of inhibiting TGF-beta signaling through its association with the Smad proteins. However, new studies suggest that SKI plays additional roles not only inside but also outside the nucleus. In normal melanocytes and primary non-invasive melanomas, SKI localizes predominantly in the nucleus, whereas in primary invasive melanomas SKI displays both nuclear and cytoplasmic localization. Intriguingly, metastatic melanoma tumors display nuclear and cytoplasmic or predominantly cytoplasmic SKI distribution. Cytoplasmic SKI is functional, as it associates with Smad3 and prevents its nuclear localization mediated by TGF-beta. SKI can also function as a transcriptional activator, targeting the beta -catenin pathway and activating MITF and NrCAM, two proteins involved in survival, migration and invasion. Intriguingly, SKI appears to live a dual life, one as a tumor suppressor and another as a transforming protein. Loss of one copy of mouse ski increases susceptibility to tumorigenesis in mice, whereas its overexpression is associated with cancer progression of human melanoma, esophageal, breast and colon. The molecular reasons for such dramatic change in SKI function appear to result from new acquired activities. In this review, we discuss the mechanisms by which SKI regulates crucial pathways involved in the progression of human malignant melanoma.
Cancer Metastasis Rev 2005 Jun
PMID:SKI pathways inducing progression of human melanoma. 1598 36

To understand immune responses to human cancer and develop more effective immunotherapy, human tumor antigens has been isolated using various immunological methods with tumor reactive T cells or antibodies obtained from patients with melanoma. During the process of tumor antigen isolation, various molecules with genetic alterations or over-expression in tumor cells, which may be involved in proliferation, differentiation, or survival of various cancer cells, were identified. In melanoma, abnormal molecules with mutations including beta -catenin, CDK4, and BRAF, and molecules with increased expression including Survivin, were immunologically detected. Therefore, immunological isolation of human tumor antigens contributes to the identification of important molecules including altered signaling molecules involved in melanoma formation.
Cancer Metastasis Rev 2005 Jun
PMID:Immunological detection of altered signaling molecules involved in melanoma development. 1598 43

In this review the role of the epithelial E-cadherin/catenin complex in cases of laryngeal cancer is discussed. Cancer of the larynx remains the second most common head and neck malignancy. The E-cadherin/catenin complex expression is abnormal in laryngeal squamous cell carcinomas. Loss or reduction of E-cadherin expression is especially observed in supraglottic larynx cancer in relation with poor histological differentiation and/or lymph nodes metastases. Controversial results in some studies regarding the role of the E-cadherin/catenin complex in various anatomical parts of the larynx have been reported. Further studies are needed to establish the importance of the E-cadherin/catenin complex as a potential biomarker in laryngeal cancer diagnosis and prognosis.
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PMID:The role of E-cadherin/catenin complex in laryngeal cancer. 1640 43

The histological features that accompany the development and progression of solid tumors are known to be controlled by a distinct cascade of molecular events. One such event is the inactivation of tumor suppressor genes, such as the adenomatous polyposis coli (APC) gene. Disruption of the cadherin-catenin cell adhesion complex also plays a role in the initial steps of cancer invasion and metastasis whereas alterations in cell structural molecules, such as tubulin, may contribute to the cancer phenotype. The understanding of the status of these molecules in ESSC may provide novel markers that could impact on management of the disease. The present study examined alterations in the microsatellite sequence of the APC gene via fluorescent-based polymerase chain reaction in 100 cases of primary esophageal squamous cell carcinoma. In addition, the expression of E-cadherin, alpha- and beta-catenin, and alpha- and beta-tubulin was analyzed using immunohistochemistry. These data were then statistically compared with each other as well as the relevant clinicopathologic data. Although the APC markers (D5S210, D5S346, D5S299, and D5S82) tested did show an overall high frequency of allelic imbalance/loss of heterozygosity (62.48%) and microsatellite instability (41.27%), they did not show prognostic significance in the study cohort and were not correlated with the immunohistochemical data. The tubulin proteins showed no significant change in expression in the tumor tissue The decreased immunoreactivity of E-cadherin was statistically correlated with the presence of lymph node metastases (P = .0180). Although alpha- and beta-catenin as well as E-cadherin showed no direct prognostic value, E-cadherin may warrant further investigation as an indirect prognostic indicator by allowing more accurate prediction of lymph node metastases.
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PMID:Microsatellite analysis of the APC gene and immunoexpression of E-cadherin, catenin, and tubulin in esophageal squamous cell carcinoma. 1642 11


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