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

Mutations of the p53 tumor-suppressor gene are the most common genetic alterations in human cancer, found in approximately 50% of all tumors. The importance of p53 in human cancer attracts attention in molecular studies dealing with the pathogenesis, diagnosis and prognosis in tumor pathology. This review summarizes the current understanding of p53 both on the genetic and protein level. Frequency and spectrum of somatic p53 mutations in the carcinogenesis of breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, squamous-cell carcinoma of the skin and malignant melanoma are discussed including our own investigations and studies published in the literature.
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PMID:[Tumor suppressor gene p53. Theoretical principles and their significance for pathology]. 871 Jul 88

We analysed the relationship between several biological properties of gastric cancers and their chemosensitivity determined by MTT assay. Higher chemosensitivity was associated with poor differentiation, aneuploidy, and higher proliferative activity. Lymph node metastasis was more chemosensitive than primary lesion, while liver metastasis was less. Gastric cancer expressing multidrug-resistance associated protein (MRP) showed lower sensitivity to several anticancer drugs, including adriamycin and etoposide. p53 status and susceptibility to apoptosis were also associated with chemosensitivity. Thus, chemosensitivity of clinical gastric cancer might be increased if these characters can be modified by some new biologic therapy.
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PMID:[Biological features determining the chemosensitivity of gastric cancer]. 872 Oct 85

The role of oncogenes and tumor suppressor genes in the pathogenesis of gastric cancer has recently received considerable attention. p53 is a tumor suppressor gene that is essential in the cell cycle; it prevents G1/S phase transition, after exposure to ionizing radiation or DNA-damaging chemotherapy. This allows the cell to repair its DNA or, if the damage is irreversible, to elicit apoptotic cell death. p53 mutations are seen in many human tumors including gastric carcinoma. Evidence suggests that mutant p53 is associated with shorter life expectancy in gastric, breast, lung, and colorectal cancer. A number of studies have shown cellular resistance to chemotherapy in the presence of mutant p53. Currently, increasing interest has been devoted to the potential role of mutant p53 as a screening tool.
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PMID:Genomania of p53 protein in gastric cancer. 872 51

Expression of bcl-2 is most commonly associated with the t(14;18) translocation present in most folicular lymphomas (1). More recently, bcl-2 oncoprotein has been identified in normal tissues and in nonhematologic malignancies. In this study, we investigate the use of bcl-2 as a marker to distinguish metastatic breast carcinoma from primary lung and gastric cancers, and we evaluate the role of bcl-2 as an independent prognostic factor in breast carcinoma and its relationship to other breast cancer markers. bcl-2 immunostains were done on 371 adenocarcinomas of the breast, lung, and stomach. Additionally, 231 samples of metastases from patients with breast or gastric cancer were evaluated for bcl-2 expression. All breast cancer tissue samples had immunohistochemical data on expression of estrogen and progesterone receptors, p53, neu/cerb2, and MIB-1. A large proportion (79.3%) of invasive breast carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary and gastric carcinomas did. Moreover, staining was moderate to intense in 70.2% of the breast cancers, compared with only one specimen of lung carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate staining. There was agreement of bcl-2 expression between primary and metastatic sites in all specimens except one. Expression of bcl-2 in breast adenocarcinomas was significantly associated with hormone receptor positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-positive specimens were estrogen receptor negative and 24.2% of bcl-2-positive specimens were progesterone receptor negative. Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer. We conclude that adenocarcinomas with intense bcl-2 staining are more likely to be of breast than of pulmonary or gastric origin. We recommend the addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP-15, and S100) that might contribute to the identification of a larger proportion of metastatic breast carcinomas, because almost one-half of the estrogen-receptor negative cancers were bcl-2 positive.
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PMID:Expression of bcl-2 by breast cancer: a possible diagnostic application. 872 86

The presence of the nuclear phosphoprotein p53 was investigated in a series of 120 consecutive gastric carcinomas. This immunohistochemical study on formalin-fixed, paraffin-embedded material found p53 expression in 43 per cent (n = 51) of carcinomas using a monoclonal antibody (DO-1), whereas no immunoreactivity for p53 was present in tumour-associated non-neoplastic gastric mucosa or tumour stroma. There was no statistically significant correlation with known prognostic parameters such as extent of tumour growth (pT state), nodal involvement (pN state), or tumour grade. The same applied for association with patient age and sex or pathological parameters such as tumour size, localization, or growth pattern according to histological classification. Kaplan-Meier analysis revealed marginal statistically significant differences in survival times between patients with p53-positive tumours with more than 35 per cent of p53-positive tumour cells and those with less than 35 per cent of p53-positive tumour cells or p53-negative tumours (P = 0.04). However, by multivariate analysis, p53 immunoreactivity did not turn out as an independent prognostic parameter. p53 expression can easily be detected in a variety of human malignancies including gastric cancer by immunohistochemical methods, but its prognostic significance and possible role as an independent marker of poor prognosis still have to be confirmed by further studies.
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PMID:Prognostic influence of p53 expression in gastric cancer. 915 24

Chromosome 17 and p53 gene locus alterations were determined on 67 gastric carcinomas by dual-color fluorescence in situ hybridization, using probes for centromere 17 and the 17p13.1 (p53 locus). The results were compared with loss of heterozygosity (LOH) at 17p13.3, direct sequencing of exons 5 to 9 of p53, and nuclear overexpression of p53 protein. Deletion of p53 was found in 26 of 67 tumors (39%). All 26 also showed LOH at 17p13.3, frequently overexpressed p53 protein, and had polysomy 17. The functional loss of p53 gene in these tumors, 85% of which were of intestinal type, appears to be caused by both deletion of 17p13.1 and missense mutation of the remaining allele. There were 9 tumors that had neither deletion nor LOH but had a large proportion of cancer cells that overexpressed p53 election. Despite evidence of LOH, there was no p53 deletion in 11 tumors. Finally, 21 tumors, mostly of diffuse type, showed neither deletions, LOH, nor p53 overexpression. Our data suggest that in gastric cancer, deletion of 17p is principally responsible for the allelic loss at the p53 gene and that analysis of deletions by the dual-color fluorescence in situ hybridization is a sensitive and useful approach to clarify chromosomal aberrations.
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PMID:Analysis of chromosome 17p13 (p53 locus) alterations in gastric carcinoma cells by dual-color fluorescence in situ hybridization. 890 47

Genetic instability, alterations of tumor suppressor genes as well as activation of oncogenes and aberrant expression of growth factor/receptor system found in human stomach carcinogenesis are overviewed. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and amplification of the cyclin E gene are common events of both well differentiated and poorly differentiated gastric carcinomas. K-ras mutations, c-erbB2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC, LOH of the bcl-2 gene and LOH at DCC locus are preferentially associated with well differentiated gastric cancer. On the other hand, microsatellite instability, reduction or loss of cadherin and catenins, K-sam and c-met gene amplification confer the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cell-adhesion molecules in the c-met expressed cancer cells and hepatocyte growth factor from stromal cells is involved in morphogenesis of gastric cancer.
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PMID:[Multistep stomach carcinogenesis]. 892 Jun 75

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.
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PMID:Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG). 895 93

The aim of this paper is to review the most frequent genetic alterations found in gastric carcinoma, and to focus on the main differences between intestinal and diffuse cancer types. Particular emphasis will be given to tumor suppressor genes, above all to p53. The role of normal and mutated p53 proteins has been studied in depth in a variety of cell types, and p53 alterations have been extensively analysed in many human tumors, including gastric cancer. Accordingly, the paper will report p53 data on this neoplasia, and consider these data in the light of various more general notions.
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PMID:Genetic alterations in gastric cancer. 896 13

The expression of the p53-inducible cyclin-dependent kinase inhibitor p21WAF1/CIP1 in non-neoplastic mucosa, adenoma, and adenocarcinoma of the stomach was examined immunohistochemically and its relationship with p53 expression and proliferative activity was analysed. In normal gastric mucosa as well as in intestinal metaplasia the epithelial cells at the surface which showed no proliferative activity expressed p21WAF1/CIP1, whereas the cells in the deep area of the glands expressing Ki-67 did not. In the neoplastic lesions, the expression of p21WAF1/CIP1 was detected in 78 per cent (112/144) of the adenomas and 76 per cent (262/343) of the adenocarcinomas. The incidence of p21WAF1/CIP1 expression did not differ among histological types of gastric carcinoma. The strong expression of p21WAF1/CIP1 was more frequently observed in carcinomas invading into submucosa or in cases of stages 2, 3, and 4 than in carcinomas limited to the mucosa or in stage 1 cases. The incidence of strongly positive cases was higher in carcinomas with lymph node metastasis than in those without metastasis. There was no apparent correlation between the expression of p21WAF1/CIP1 and the abnormal accumulation of p53 or with proliferative activity measured by Ki-67 expression. These findings overall suggest that p21WAF1/CIP1 might be associated with the senescence of non-neoplastic gastric epithelial cells; that a p53-independent pathway might be substantially involved in the induction of p21WAF1/CIP1 in gastric neoplasia; and that the proliferative activity of gastric cancer might not be solely dependent on control of the cell cycle by p21WAF1/CIP1.
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PMID:Expression of cyclin-dependent kinase inhibitor p21WAF1/CIP1 in non-neoplastic mucosa and neoplasia of the stomach: relationship with p53 status and proliferative activity. 897 68


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