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)

Reduced expression of E-cadherin, a cell-cell adhesion molecule, is observed in oesophageal adenocarcinomas and correlates with less favourable pathological parameters and survival. To determine if genetic events lead to reduced E-cadherin expression in these patients, we screened all 16 exons of the E-cadherin gene for mutations with the polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) technique in 49 resection specimens, including four loco-regional lymph node metastases, four established cell lines and four xenografts. Fifteen exon-spanning primer pairs were used, and in nine amplicons aberrant bands were detected. Sequencing of the amplicons revealed a one base-pair deletion (codon 120; exon 3) in cell lines JROECL 47 and JROECL 50 leading to a premature downstream stop codon. Polymorphisms were identified for amplicons 1, 4/5, 11, 12, 13, 14 and 16 corresponding with data from the literature. Three new polymorphisms were detected for amplicons 2, 3 and 4/5. Loss of heterozygosity (LOH) of the E-cadherin locus on 16q22.1 was examined with four polymorphic markers. LOH was found in 31 of the 48 informative cases (65%). These results show that, despite the frequent LOH of the E-cadherin locus, mutations in the E-cadherin gene are rare events and can not be held responsible for down-regulation of E-cadherin observed in the majority of adenocarcinomas of the oesophagus.
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PMID:E-cadherin gene mutations are rare in adenocarcinomas of the oesophagus. 1040 14

E-cadherin is a cell-cell adhesion molecule expressed predominantly by epithelial cells. Reduction or loss of E-cadherin immunoreactivity has been associated with tumour progression in many epithelial cancers, including bladder carcinomas. The fibroblast growth factor receptor 2b (FGFR2b) recognized specifically by FGF7 is expressed only by epithelial cells. Recently, decreased expression of FGFR2b protein and mRNA was found to be associated with tumour progression in bladder carcinomas. The purpose of this investigation was to look for a possible relationship between E-cadherin and FGFR2b expression in bladder carcinomas. As decreased E-cadherin immunoreactivity was found to correlate directly with decreased expression at the mRNA level, the possible relationship between E-cadherin and FGFR2b was investigated at the mRNA level using semi-quantitative RT - PCR in 92 transitional cell carcinomas (TCCs) and four lymph node metastases. All tumours with low E-cadherin expression had low expression of FGFR2b, whereas tumours with low FGFR2b mRNA could express any level of E-cadherin mRNA. The same observation was equally valid for bladder and colon cancer cell lines suggesting that, besides bladder tumours, this relationship could apply to other carcinomas types. These results suggest that a relationship exists between the transcription of the E-cadherin and FGFR2b genes preventing high expression of FGFR2b where expression of E-cadherin is low. We suggest that reduced expression of FGFR2b in conjunction with decreased expression of E-cadherin may contribute to the aggressive behaviour attributable to high grade TCCs.
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PMID:Relationship between E-cadherin and fibroblast growth factor receptor 2b expression in bladder carcinomas. 1052 52

The outcome of breast carcinoma is usually determined by multiple factors. Aberrant expression of the cell adhesion molecule CD 44 has been claimed to be associated with poor prognosis in various human malignancies. This study was designed to investigate any correlation between the soluble adhesion molecule CD 44 and the clinicopathologic variables and to evaluate the possible prognostic significance of soluble CD 44. Venous blood samples were preoperatively collected from 100 patients with invasive breast carcinoma. The serum levels of different soluble CD 44 molecules (CD 44 standard form and CD 44 splice variant V6) were measured with an enzyme immunoassay method. The data of primary tumor status, age, estrogen receptor status, lymph node status, histologic grading, distant metastases status, TNM staging, S-phase fraction, and ploidy pattern were collected and evaluated simultaneously with the serum levels of soluble CD 44 st and CD 44 V6. Twenty healthy subjects were used as the control group. The serum levels of soluble CD 44 st showed no significant elevation in patient group. The mean value of soluble CD 44 V6 in patient group was 269.2 +/- 94.3 ng/ml and that of the control group was 179.5 +/- 50.7 ng/ml; the difference was significant (p < 0.01). In multivariate analysis, distant metastasis (p < 0.05) and TNM staging (p < 0.01) appeared as independent factors regarding the significant higher serum levels of soluble CD 44 V6. Based on our preliminary results, preoperative serum soluble CD 44 V6 is closely related to distant metastases and TNM staging. The possible role of soluble CD 44 V6 in the prognostic value of breast carcinoma deserves further elucidation and evaluation with long-term patient follow-up.
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PMID:Evaluation of the prognostic value of serum soluble CD 44 in patients with breast cancer. 1059 65

In-frame deletions from the E-cadherin mRNA, coding for a homophilic cell adhesion molecule, are characteristic for diffuse-type gastric carcinomas. Using immunohistochemical analysis the mutant form cannot be distinguished from normal E-cadherin, making results difficult to interpret. In this study, a rat monoclonal antibody, designated E-cad delta 9-1, was generated against a peptide spanning the fusion junction region between exons 8 and 10. This new epitope is present in an E-cadherin variant that lacks exon 9 from the mRNA due to different splice-site gene mutations. Using Western blotting and immunohistochemistry of E-cadherin-transfected cells, we demonstrate that E-cad delta 9-1 specifically reacts with E-cadherin lacking exon 9 but not with the wild-type protein. No immunoreactivity was observed in 31 nontumorous and embryonal tissues analyzed. In gastric carcinoma specimens known to express mutant E-cadherin mRNA lacking exon 9, E-cad delta 9-1 targets exclusively tumor cells in routine formalin-fixed and paraffin-embedded material from biopsies, primary tumors, and lymph node metastases. In a retrospective series of 172 diffuse-type gastric carcinomas expressing E-cadherin, E-cad delta 9-1 reacted with 22 tumors (13%). This new tumor marker-monoclonal antibody system could open novel avenues for selective diagnosis and specific therapy of a subgroup of diffuse-type gastric cancer patients.
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PMID:Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody. 1059 8

To investigate the relationship between the expression of the cell adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) in uveal melanoma and the metastatic spread in the first 5 years after diagnosis, we performed a hospital-based case-control study with human tissue from 90 patients who underwent enucleation for primary uveal melanoma (iris melanoma excluded). Thirty-five patients developed metastasis within the first 5 years, and 55 patients lived metastasis-free for at least 5 years after enucleation. The paraffin-embedded and formalin-fixed globes were studied by immunohistochemistry with monoclonal antibodies for ICAM-1, VCAM-1 and NCAM. A strong ICAM-1 positivity (more than 75% of the tumor cells stained positive) was detected in 73 tumors (81%). The expression of 75% or less ICAM-1 positive cells in tumors was strongly associated with the development of metastases (odds ratio: 7.5, p = 0.001). Multiple logistic regression models showed that ICAM-1 is an independent risk factor for metastasis even after control for important prognostic markers like extraocular growth, ciliary body involvement, scleral infiltration and cell type. VCAM-1 was expressed in 24 out of 88 tumors (27.3%) and NCAM only in 14 out of 87 tumors (16%). Only spindle cells stained positive with anti-NCAM. NCAM and VCAM-1 expression was not related to metastasis. Our results show that the loss of ICAM-1 expression is associated with an increased risk of metastasis within the first 5 years after diagnosis.
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PMID:Expression of the cell adhesion molecules ICAM-1, VCAM-1 and NCAM in uveal melanoma: a clinicopathological study. 1064 45

E-cadherin is a homophilic cell adhesion molecule that is mutated in half of diffuse-type gastric cancer patients. Since these mutations generally affect the extracellular portion of the transmembrane molecule and do not interrupt the reading frame, altered E-cadherin protein may be an excellent tumor marker. We established a rapid PCR-based E-cadherin mutation detection technique allowing positive results within a day. Furthermore, we succeeded in the generation of monoclonal antibodies that specifically react with mutant E-cadherin but not with the wild-type protein. In gastric carcinoma specimens known to express mutant E-cadherin messenger RNA these monoclonal antibodies target exclusively tumor cells in routine formalin fixed and paraffin embedded material from biopsies, primary tumors and lymph node metastases. Non-tumorous cells, including normal gastric epithelium expressing wild-type E-cadherin, are not stained. The unique type of E-cadherin mutations in diffuse-type gastric cancer (missense mutations and complete or partial in-frame deletions of exons) might improve the information of conventional diagnostic techniques. In addition, they may open novel and more selective clinical avenues to treat small tumor deposits for adjuvant-, neoadjuvant- and additive-therapy.
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PMID:[Diffuse stomach carcinoma: from H&E diagnosis and molecular pathology to specific therapy]. 1071 5

The GA733-2 gene encodes the epithelial glycoprotein 40, a homophilic cell-cell adhesion molecule, which is expressed on the surface of epithelial cells and associated with a variety of carcinomas, e.g. breast, colorectal and lung carcinomas. To test if it could serve as a tumor marker, we have analysed the expression of GA733-2 in bone marrow (BM) and peripheral blood (PB) from healthy donors, and of patients with haematological malignancies or breast cancer using reverse transcriptase-polymerase chain reaction (RT-PCR). The GA733-2 nested PCR was positive in 100% (8/8) of BM and 40% (16/40) of PB from healthy donors, in 100% (33/33) of BM from patients with breast cancer who had no evidence of distant metastases and also in BM and PB from patients with haematological malignancies. GA733-2 mRNA is not specific as a marker for the detection of breast cancer cells in BM and PB.
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PMID:Evaluating GA733-2 mRNA as a marker for the detection of micrometastatic breast cancer in peripheral blood and bone marrow. 1072 19

The cell adhesion molecule E-cadherin is expressed on the basolateral surfaces of normal mammary epithelial cells and is lost in a subset of breast cancers. Loss of E-cadherin expression has been postulated to facilitate tumor cell detachment from a primary tumor ultimately leading to metastasis. In this paper, I review the published in vitro data that initially supported this "invasion suppressor" role for E-cadherin as well as more recent in vitro and in vivo data showing that E-cadherin-positive tumor cells can metastasize. I examine other molecules required for E-cadherin function and discuss how defects in the expression or function of these molecules might alter E-cadherin function in E-cadherin-positive tumor cells. For example, loss of expression or function of catenins, intracellular molecules that interact with E-cadherin, can result in the loss of E-cadherin-mediated adhesion and a more invasive phenotype. Altered phosphorylation of E-cadherin or catenins can also influence E-cadherin function. Finally, expression of other cell surface molecules such as mucins may interfere with E-cadherin function. The collective effect of these molecules on the adhesive phenotype of breast cancer cells may be one determinant of metastatic potential.
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PMID:The role of cadherin-mediated adhesion in breast cancer. 1088 95

CD44, belongs to the cell adhesion molecule family and is expressed on cell surfaces in several isoforms which are generated by alternative splicing of messenger RNA. These splice variants have been shown in several cancer cell types and are thought to be involved in tumor progression. The aim of the current study was to evaluate the expression of selected CD44 variants on lung cancer cells of various histology and to compare these with other markers of tumor spread. Surgical samples of primary lung carcinoma of various histology were subjected to alkaline phosphatase-anti-alkaline phosphatase complex immunohistochemistry using a panel of monoclonal antibodies: anti-CD44 v5, v6, v7/8, v10, anti-Ki-67, anti-Bcl-2 and anti-p53. Positive cells were scored in a semiquantitative way. The patients were subdivided into groups with and without metastases, as found during surgery. All CD44 variants tested could be demonstrated on lung cancer cells, but the incidence of particular isoforms varied, depending on lung cancer histology. In general, CD44 expression was highest in squamous cell tumors and lowest in anaplastic small cell carcinomas. Squamous cell cancers had high expression of v5 and v6 variants, while in anaplastic large cell and small cell carcinomas v10 was abundant. When Ki-67, Bcl-2 and p53 protein expression was compared to the incidence of CD44 variants, coincidence was found for v10 only. Most of the cases positive for v10 were also Ki-67 positive (p = 0.0146). In 12 cases with metastases, tumor cells had high v6 and Ki-67 expression, but these data were not significant compared to cases without metastases. Overall, these data suggest that v5 and v6 variants are of significance in squamous cell lung carcinoma, presumably in the promotion of metastasis, while in anaplastic small cell or large cell cancers only v10 expression seems to correlate with proteins associated with tumor growth and progression.
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PMID:Isoform expression of CD44 adhesion molecules, Bcl-2, p53 and Ki-67 proteins in lung cancer. 1105 26

Primary pulmonary adenocarcinoma was studied, looking for relationships between the expression of cell adhesion molecules (CAMs) E-cadherin, beta-catenin and CD44v6, and clinicopathological tumour parameters and patient post-operative survival. Formalin-fixed, paraffin-embedded tissue from 120 primary lung adenocarcinomas, including 23 poorly differentiated tumours, 17 of probable bronchial origin, and 29 with a prominent bronchioloalveolar pattern, together with nodal metastatic tumour from 34 of these patients was stained using monoclonal antibodies and immunohistochemistry. Sections were scored either high level (>10% cells positive) or low level (<10% positive). High level expression of CD44v6 was retained in 28.4% (34/120) of tumours, while high levels of E-cadherin (57.5%, 69/120) and beta-catenin (80. 8%, 97/120) were more frequent. For all CAMs, staining levels did not correlate with nodal status, stage or tumour type. The apical or basal staining seen in normal bronchial and alveolar epithelium was often seen in papillary, glandular, and bronchioloalveolar areas of tumour, while solid invasive tumour more often showed pericellular staining. When the staining for each CAM in 34 nodal metastases was compared with that in the corresponding primary tumour, a high degree of concordance was found, with no tendency for metastases to show less staining than the primary tumour. Expression of E-cadherin and beta-catenin in the primary tumour had no influence on post-operative survival, but patients whose tumours had low level CD44v6 expression had a poorer post-operative survival than those with high levels of CD44v6 (p=0.0014 for all patients, p=0.0012 for stage I patients only). In primary pulmonary adenocarcinoma, the levels of expression of E-cadherin, beta-catenin, and CD44v6 are not associated with lymph node metastases or tumour stage but the staining pattern is associated with tumour morphology. Low levels of CD44v6 expression predict a poor post-operative survival, independently of stage, while there is no such relationship with the expression of E-cadherin or beta-catenin.
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PMID:Expression of CD44v6 but not E-cadherin or beta-catenin influences prognosis in primary pulmonary adenocarcinoma. 1111 58


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