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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-Cadherin alterations have been reported frequently in sporadic diffuse type gastric and lobular breast carcinomas. Germline mutations of this gene have been identified recently in several gastric cancer families. We analyzed seven patients with a family history of the disease who had diffuse type gastric cancer diagnosed before the age of 45 for germline mutations in CDH1, the gene encoding the E-cadherin protein. We identified a frameshift mutation in exon 3 in one patient with a strong family history of gastric cancer. The same germline mutation was found in the patient's mother, who had metachronous development of lobular breast and diffuse type gastric carcinomas. Immunohistochemistry for E-cadherin protein expression revealed an abnormal staining pattern in both of these tumors, suggesting complete inactivation of the cell adhesion molecule. Thus, our finding suggests that besides diffuse type gastric cancer, lobular breast carcinomas may be associated with germline CDH1 mutations.
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PMID:Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. 1043 26

Tumor cells in abdominal lavage specimens from patients with gastric carcinoma strongly predict subsequent peritoneal metastasis and poor prognosis. Reverse transcription (RT)-polymerase chain reaction (PCR) detection of wild-type E-cadherin has been claimed to be superior to conventional cytology for the detection of patients who subsequently develop peritoneal metastases. The present study tested this hypothesis and determined whether or not the detection of mutated, tumor-specific E-cadherin messenger RNA in abdominal lavage specimens serve as a useful diagnostic tool. Preoperative lavage specimens from 52 patients with diffuse-type gastric carcinoma and from 5 patients with benign disease were analyzed by conventional cytology and by RT-PCR for amplification of E-cadherin. Tumor cells were detected by cytology in 8 (15.3%) of the 52 patients with gastric cancer. The E-cadherin was detected in all 57 samples by RT-PCR. Two of these had abnormal E-cadherin amplification products confirmed to be mutations by direct sequencing, which were identical in the primary tumors. These findings suggest that the detection of wild-type E-cadherin is not sufficiently tumor specific. Also, for diffuse gastric carcinomas with confirmed E-cadherin mutations, detection of mutant E-cadherin by RT-PCR is a potentially valuable method for tumor cell detection in lavage specimens.
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PMID:Rapid detection of mutated E-cadherin in peritoneal lavage specimens from patients with diffuse-type gastric carcinoma. 1047 80

To extend earlier observations of germline E-cadherin mutations in kindreds with an inherited susceptibility to diffuse gastric cancer, we searched for germline E-cadherin mutations in five further families affected predominantly by diffuse gastric cancer and one family with a history of diffuse gastric cancer and early-onset breast cancer. Heterozygous inactivating mutations were found in the E-cadherin gene in each of these families. No mutation hotspots were identified. These results demonstrate that germline mutation of the E-cadherin gene is a common cause of hereditary diffuse gastric cancer and suggest a role for these mutations in the incidence of breast cancer.
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PMID:E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. 1047 33

The aim of this study was to elucidate the pathogenetic backgrounds of early-onset gastric cancers. Mutations of the E-cadherin and beta-catenin genes were analyzed by subjecting microdissected cancer cells and corresponding non-cancerous epithelial cells obtained from 9 gastric cancer patients under 35 years old to polymerase chain reaction-single strand conformation polymorphism analysis. Somatic, but no germline, E-cadherin gene mutations were detected in 6 (67%) of the patients. The cancer cells of 2 patients were exon 9-deleted E-cadherin molecule-immunoreactive. Neither somatic nor germline mutations in exon 3 of the beta-catenin gene were observed in any patient. One patient lacked beta-catenin immunoreactivity and the cancer cells of 6 others showed cytoplasmic beta-catenin immunoreactivity. The E-cadherin-mediated cell adhesion system in the cancer cells of all the patients examined appeared to be disrupted, indicating that somatically acquired dysfunction of this system plays an important role in early-onset diffuse-type gastric cancers. Helicobacter pylori infection was observed in 6 (67%) of our 9 patients, an incidence higher than the average in young Japanese individuals. Thus, early-onset gastric cancers may be attributable to environmental factors such as Helicobacter pylori infection.
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PMID:Disruption of E-cadherin-mediated cell adhesion systems in gastric cancers in young patients. 1055 30

Families with autosomal dominant inherited predisposition to gastric cancer have been described. More recently, germline E-cadherin/CDH1 mutations have been identified in hereditary diffuse gastric cancer kindred. The need to have protocols to manage and counsel these families in the clinic led a group of geneticists, gastroenterologists, surgeons, oncologists, pathologists, and molecular biologists to convene a workshop to produce consensus statements and guidelines for familial gastric cancer. Review of the available cancer pathology from people belonging to families with documented germline E-cadherin/CDH1 mutations confirmed that the gastric cancers were all of the diffuse type. Criteria to define the different types of familial gastric cancer syndromes were agreed. Foremost among these criteria was that review of histopathology should be part of the evaluation of any family with aggregation of gastric cancer cases. Guidelines for genetic testing and counselling in hereditary diffuse gastric cancer were produced. Finally, a proposed strategy for clinical management in families with high penetrance autosomal dominant predisposition to gastric cancer was defined.
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PMID:Familial gastric cancer: overview and guidelines for management. 1059 93

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

beta-catenin, a component of the E-cadherin-catenin cell adhesion complex, also plays a separate intracellular signalling role, interacting with APC protein. Intracellular accumulation of beta-catenin is common in colorectal neoplasia. beta-catenin abnormalities are associated with poor survival in gastric cancer, but previous studies do not differentiate between membrane-associated and intracellular beta-catenin. In this study we aimed to determine which type of expression abnormalities for E-cadherin, beta-catenin and alpha-catenin correlate with clinico-pathological features and survival in gastric cancer. Immunoperoxidase staining of paraffin-embedded sections from 40 gastric cancers was performed for E-cadherin, alpha- and beta-catenins using microwave unmasking and an avidin-biotin technique. Clinical data were obtained from case records and cancer registry records. Reduced membranous expression of beta-catenin occurred in 10/12 (83%) diffuse and 8/28 (29%) intestinal tumours (P= 0.0014), and was associated with poor differentiation (P= 0.0015) and short survival (P= 0.032), but not with age, sex, tumour size or nodal status. Nuclear expression of beta-catenin was uncommon; cytoplasmic expression was observed in 13/40 cases (33%) but did not correlate with histology, tumour grade or survival. Reduced E-cadherin membrane expression was associated with lymph node metastasis (P= 0.02). Neither E-cadherin or alpha-catenin expression correlated with survival. Reduced membranous expression of beta-catenin predicts poor prognosis in gastric cancer, whilst ectopic intracellular expression is relatively rare. The apparent differences in beta-catenin expression from those found in colon cancer merit further study.
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PMID:Reduction in membranous expression of beta-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer. 1060 38

Gastric cancer, the second most common cancer in the world, kills about one million people a year, almost half of whom are Chinese. Chinese, Japanese and Koreans as well as east Europeans top the list with over 40 per 100,000 population per year, with a wide margin over Americans, Indians and Zimbabweans in whom the rates are below 1 per 100,000. The excellent prognosis of early gastric cancer is well established, and survival of cancer involving beyond the submucosa remains poor and there is little new in management. However, recent years have witnessed a breakthrough in the understanding of causative factors and molecular genetic abnormalities in gastric cancer that should pave the way for prevention, early detection and prognostication. Established carcinogens for gastric cancer now include Helicobacter pylori and N-nitroso compounds; other causative factors include salt and salted food intake, cigarette smoking, male sex, and familial genetic abnormalities. H. pylori infection increases cancer risk by about 5 in a 10-year period. Diet high in salt carries a relative risk of up to 6, and a highly significant correlation between 24 h urinary salt content and incidence of gastric cancer has been shown in 24 countries. The risk from smoking and male sex is under 2. Many N-nitroso compounds, which come from nitrites, which in turn come from nitrates in food following bacterial transformation in a hypochlorhydric environment, are established carcinogens in animals, but their risk for human gastric cancer is still debatable. The intestinal type of gastric cancer, according to Correa's hypothesis, develops from chronic inflammation leading to intestinal metaplasia, dysplasia and cancer, and is more associated with H. pylori and early gastric cancer. The diffuse type of gastric cancer does not go through these precancerous conditions and moves straight from inflammation to cancer. Associated with inflammation are an increase in proliferation and apoptosis, and this fine balance between proliferation and apoptosis may be uncoupled by genetic mutations. It is believed that as a result of the accumulation of molecular genetic abnormalities, a cancer eventually develops and metastasizes. p53 mutation, cyclin overexpression (especially in intestinal type), microsatellite instability, down regulation of E-cadherin (especially in diffuse type), and telomerase reactivation are some prominent examples. These molecular abnormalities have the potential for screening, early detection and prognostication. Fruits and vegetables, green tea, alpha-tocopherol and other micronutrients such as selenium have been shown to reduce the risk for gastric cancer. In fact, it has been reported that diet consisting of vegetables and fruits, low in salt, together with the avoidance of cigarette smoking would prevent two-thirds to three-quarters of gastric cancer. Furthermore, eradication of H. pylori, and for that matter future vaccination, has the theoretical potential of preventing gastric cancer, and the potential use of COX2 inhibiting NSAID in inducing apoptosis may reverse precancerous conditions of the stomach. Both approaches are being intensely studied.
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PMID:9th Seah Cheng Siang Memorial Lecture: gastric cancer--where are we now? 1067 11

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral, and there is evidence that it is associated with an elevated familial risk of breast cancer. Although women with LCIS suffer an increased risk of invasive breast disease, this risk is moderate suggesting that LCIS may result from mutation of a gene or genes conferring a high risk of LCIS, but a lower risk of invasive breast cancer. The high frequency of somatic mutations in E-cadherin in LCIS, coupled with recent reports that germline mutations in this gene can predispose to diffuse gastric cancer, raised the possibility that constitutional E-cadherin mutations may confer susceptibility to LCIS. In order to explore this possibility we have examined a series of 65 LCIS patients for germline E-cadherin mutations. Four polymorphisms were detected but no pathogenic mutations were identified. The results indicate that E-cadherin is unlikely to act as a susceptibility gene for LCIS.
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PMID:Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene. 1068 67

The topographical organisation of the epithelium lining mucous membranes has been an intense point of research. One of the fundamental biological issues underpinning this and associated issues relates to the role and regulation of epithelial adhesion molecules. Adhesion between individual cells allows an intact layer to be formed, which is selectively permeable. In addition, the orchestrated regulation of multiple adhesion molecules allows the gradual transition from basal secretory cells to apical absorptive cells in the crypt-villus gradient. Moreover, it is becoming clear that no one class of adhesion molecule can sufficiently govern crypt architecture; however, the main cell-cell adhesion molecules are the cadherins and the related desmosomal cadherins. These latter molecules interact with the catenins, which bind directly or indirectly with cytoskeletal molecules such as Rho and Rac. In addition, other complex glycoproteins, such as the carcinoembryonic antigens, might contribute to adhesion, although their mechanisms of function are distinctly different. Integrins on the basal aspect of the cells also signal important morphoregulatory signals as a result of their binding to the extracellular maxtrix. The disruption of these physiological processes also provides a necessary and, in some cases, sufficient molecular mechanism for cancer invasion and metastasis, such as occurs in E-cadherin mutation positive familial gastric cancer.
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PMID:Cadherin adhesion in the intestinal crypt regulates morphogenesis, mitogenesis, motogenesis, and metaplasia formation. 1069 34


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