Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutation of the p53 tumour-suppressor gene in exons 5 through 8 was examined in 118 cases of gastric cancer (59 early gastric cancers and 59 advanced gastric cancers) using PCR-SSCP (polymerase-chain-reaction-single-strand-conformation polymorphism) analysis and direct sequencing. In early gastric cancer, mutations were found in 15 of 41 (37%) cases of the cohesive type, i.e., papillary adenocarcinoma, well to moderately differentiated tubular adenocarcinoma, and poorly differentiated adenocarcinoma with solid nests or focal tubular structures, but were not detected in 18 cases of the non-cohesive type, i.e., signet-ring-cell carcinoma and poorly differentiated adenocarcinoma growing in a scattered manner. In advanced gastric cancer, 25 of 59 (42%) cases of the cohesive type had p53 mutation. No significant association was found between p53 mutation and other histopathological parameters such as macroscopic classification, lymph-node involvement and depth of tumour invasion. Fifteen of 25 (60%) mutations in the advanced gastric-cancer group were accompanied by allele loss at the p53 gene locus. Eighty-three percent of mutations in early gastric cancer and 52% of mutations in advanced gastric cancer showed G:C-to-A:T transition, almost exclusively at CpG dinucleotide mutational hot spots, indicating that the spectrum of p53 mutation was similar to that of colorectal cancer. These data suggest that the p53 mutation occurs selectively in gastric cancer of the cohesive type from the intramucosal cancer stage.
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PMID:p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer. 839 33

Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki-67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur.
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PMID:Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. 843 9

Gene changes in multiple oncogenes, multiple growth factors and multiple tumor-suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well-differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer.
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PMID:Molecular mechanism of stomach carcinogenesis. 844 Jul 43

We searched for P53 mutations in gastric carcinoma by analyzing tumor DNAs from 29 patients. We detected 13 different somatic mutations in 15 patients (52%) and a biallelic polymorphism in exon 6 (5 heterozygous subjects). The somatic mutations were mainly localized in the sequences corresponding to the highly conserved domains of the protein. Twelve samples showed a single base change: 11 missense and 1 nonsense mutations. Three samples showed deletions leading to a frame shift, to the in-frame loss of 2 amino acids, and to the deletion of a splicing site. All point mutations, except one, were transitions, and 91% of them were G:C-->A:T changes. We previously analyzed this panel of tumors for allelic loss at the 17p13 chromosomal region, where the P53 gene had previously been located: the results showed an increasing incidence of allelic loss in late-stage tumors. On the contrary, in the present study no trend between P53 mutations and tumor stages was found. This observation indicates that mutation events precede allelic loss in gastric cancer. Half (54%) of the mutations occurred in samples without allelic loss, suggesting that specific mutated alleles, acting in a dominant negative fashion, can alter in vivo the P53 protein function.
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PMID:Base transitions are the most frequent genetic changes at P53 in gastric cancer. 849 24

Direct evidence of tumour seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap since it is a feature of epithelial cells that would not normally be present in bone marrow. The bone marrow of 46 patients with primary gastric cancer was examined for tumour cells, using immunocytochemical techniques and antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. The monoclonal antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no. 18) commonly present in epithelial cells. The expression of tumour-suppressor genes p53 and RB for the primary lesion was also determined using the monoclonal antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the time of primary surgery. The positive findings were related to the undifferentiated tissue type and to the prominent depth of invasion, but not to other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of invasion was limited to the mucosa. The metastatic potential to bone marrow did not relate to expressions of p53 and RB genes, or to the proliferating activity of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in bone marrow are indicative of the general disseminative capability of an individual tumour, this technique may be useful for identifying patients at high risk of metastasis from a gastric tumour.
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PMID:Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis of gastric cancer. 855 89

Although the death rate from gastric carcinoma in the US and other western communities has decreased in recent times, a similar trend has not been noted in other countries, especially S.E. Asia. Upto 95% of all malignant gastric neoplasms are adenocarcinomata, but other types of gastric cancer have evoked considerable interest in the literature. Genetic factors have been suspected of playing a pivotal role in the etiology of gastric cancer but no clear inheritance pattern has emerged and environmental influences remain the focus of many current theories of pathogenesis. Current evidence implicates the non-random involvement of certain chromosomes and related oncogenes especially Ras and p53. Genes that may predispose to gastric cancer have not been clearly implicated but some studies indicate a familial aggregation of gastric cancer. The objective of this review is to reappraise the role of genetics in the etiology of gastric cancer with special reference to relevant information for practicing clinicians.
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PMID:Genetics of gastric cancer. 857 2

Thirty-one tumor samples from selected cases of gastric carcinoma were analyzed for mutations of the p53 tumor suppressor gene. Template DNA was prepared according to the touch preparation procedure, which allowed us to isolate clusters of neoplastic cells out of a stromal cellular background to be used as a template in the amplification of target exons of the p53 locus. In our present study, by polymerase chain reaction/single strand conformation polymorphism analysis we give evidence of p53 mutations occurring in the DNA-binding core domain of the protein (exons 5 through 9), which are clustered in stages III and IV of the disease (six mutations out of seventeen samples; 35%). No p53 mutations were detected in fourteen gastric cancer samples at I and II stages. Beside the use of conventional molecular scanning procedures, our study proposes the application of the touch preparation method to increase the detection of genetic alterations in human solid tumors.
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PMID:Molecular diagnosis of p53 mutations in gastric carcinoma by touch preparation. 857 4

Resection specimens from 83 patients with primary gastric lymphoma (PGL) of B cell phenotype at stage IE and at stage IIE according to the Ann Arbor classification were investigated. Histologically, these lymphomas could be divided into four types: Type I lesions (n = 24) were entirely made up of MALT lymphoma; Type II lesions (n = 13) were predominantly MALT lymphoma containing one to a few foci of high-grade B cell lymphoma; Type III lesions (n = 22) consisted largely of high-grade lymphoma with small areas of low-grade MALT lymphoma; and Type IV lesions (n = 24) were pure high-grade B cell lymphoma, mostly of the large cell type. All patients had undergone primary gastric resection, and 14 received additional chemotherapy (n = 12), or both chemotherapy and radiotherapy (n = 2). The survival probability was significantly higher for Types I and II lymphomas than for Types III and IV tumors (P < 0.05 by the generalized Wilcoxon test). According to The General Rules for the Gastric Cancer Study by the Japanese Research Society for Gastric Cancer, the stage of disease showed a clear distinction between each of them (P < 0.01 by the generalized Wilcoxon test). This staging method seemed to serve well as a prognostic indicator. The histological typing of the PGL of the present series also seemed to correlate with the gross appearance, pathologic stage and prognosis. Furthermore, the expression of cyclin D1, bcl-2 and p53 protein, and PCNA was immunohistochemically investigated in 42 cases of the present series. Most of the low-grade PGL (Types I and II) had less than 60% PCNA-positive cells, whereas the high-grade PGL (Types III and IV) had more than 60% positive cells. In a study for cyclin D1 protein, no cases showed the nuclear staining pattern characteristic for mantle cell lymphoma, and the cytoplasmic staining frequently observed in the node-based large B cell lymphoma was seldom identified in the PGL. This discrepancy might suggest a lineage difference among the morphologically similar, but site-different, lymphomas. On the other hand, bcl-2 protein overexpression was almost equal in frequency between the gastric and node-based high-grade B cell lymphomas. This is in contrast to the reports from Western countries, in which the majority of high-grade gastric tumors were bcl-2 negative.
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PMID:Clinicopathologic study of primary gastric lymphoma of B cell phenotype with special reference to low-grade B cell lymphoma of mucosa-associated lymphoid tissue among the Japanese. 858 Nov 46

In order to ascertain whether genetic alterations occur during the early stages of gastric carcinogenesis, abnormal accumulation of p53 protein and mutation of its gene in stomach tissue showing intestinal metaplasia were investigated using immunohistochemistry and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Immunohistochemistry detected 19 foci showing nuclear accumulation of p53 protein in non-neoplastic gastric mucosa in a total of 756 sections (477 of which contained intestinal metaplasia) from 16 resected stomachs containing gastric adenocarcinomas. Of these 19 p53-positive foci, 17 were diagnosed histologically as incomplete-type intestinal metaplasia and 2 as pseudopyloric glands in the regenerative mucosa. Furthermore, 14 such foci were detected in 6 patients with multiple gastric cancers. No correlation between high-iron diamine (HID)-positive sulfomucin production and p53-positive glands was observed. The DNAs were extracted selectively from these p53-positive metaplastic glands and examined for p53 mutations by PCR-SSCP analysis followed by direct sequencing. In only 10 lesions could exons; 5 to 8 be investigated completely, and of these, 4 were shown to possess p53 mutations, which were on exon 5 in 3 cases and on exon 7 in 1 case. These results indicate that irreversible genetic changes had already occurred in morphologically non-neoplastic gastric mucosa with intestinal metaplasia, and are consistent with the hypothesis that intestinal metaplasia, especially the incomplete type, may contain precursor lesions of gastric cancer.
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PMID:p53 mutations in the non-neoplastic mucosa of the human stomach showing intestinal metaplasia. 860 55

The prevalence of multiple independent primary cancer of the stomach is high in Japanese. We hypothesized that individuals with multiple, independent gastric cancers might have a greater genetic susceptibility than persons with solitary gastric cancer at the time of diagnosis. We therefore determined the frequency of mutator phenotypes in 20 persons with independent multiple gastric cancers and 42 persons with solitary primary lesions. The mutator phenotype was determined by examining dinucleotide CA repeats at the microsatellite loci D2S136 (chromosome 2), MSX2 (chromosome 5q34), D5S82 (chromosome 5q14-21) and TP53 (chromosome 17p13.1). Although there were no significant differences between the clinical and pathological features (stage or histopathological subtype) of the two groups, the prevalence of any one microsatellite instability in patients with multiple gastric cancer was greater (65% versus 24%; P = 0.003) than in those with solitary gastric cancer. The prevalence of co-occurrence of mutator phenotype in synchronous lesions was greater than expected based on their frequency in solitary gastric cancer (12% versus 9% x 9%). Persons with advanced-stage multiple primary lesions were more likely to exhibit the mutator phenotype (P = 0.10). These findings indicate that individual predisposition for qualitative or quantitative defects in DNA repair systems significantly contribute to the simultaneous occurrence of gastric cancer in Japanese.
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PMID:Frequent co-occurrence of mutator phenotype in synchronous, independent multiple cancers of the stomach. 860 74


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