Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutated ras genes have been found to be conspicuously absent from primary tumors of the esophagus, although high expression of ras p21 oncoprotein in some esophageal squamous cell carcinomas and mutations of the Ki- and Ha-ras genes in esophageal carcinoma cell lines have been reported. In this study, we found amplification of the Ki-ras gene in four of 10 esophageal adenocarcinomas (40%). No such amplification was observed among 61 squamous cell carcinomas, one pseudosarcomatous carcinoma, and eight esophageal cell lines, nor in six adenocarcinomas of the stomach. In two samples on which immunohistochemical analysis could be performed, we found overexpression of Ki-ras proteins when compared with normal samples. This Ki-ras amplification in esophageal tumors did not correlate with any pathological feature of the tumors, with the survival of the patients, or with the presence of other genetic alterations. These findings provide the first evidence for amplification of the Ki-ras gene in human esophageal cancer, which is restricted to adenocarcinomas. We also found that six of eight adenocarcinomas had point mutations in the p53 gene; this is a considerably higher prevalence than that reported for esophageal squamous cell carcinomas. These results strongly suggest that esophageal adenocarcinomas differ from squamous cell carcinomas in their molecular genetic characteristics.
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PMID:High frequency of Ki-ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus. 851 18

The prognostic factors for esophageal cancer from the viewpoint of molecular biology are reviewed. Among several oncogenes and suppressor genes erbB, int2/hst1/Cyclin D1 and MDM2 gene amplifications are significant prognostic factors for esophageal cancer. The value of p53 mutation, and expression of matrix metalloproteinase (MMPs) in the prediction of patients' survival are controversial, so further research is needed. High expression of tumor proliferation-related factors (Ki67, PCNA, and AgNOR), abnormalities of adhesion molecule (E-Cadherin, alpha-Catenin), activation of autocrine mechanism of growth factor (EGFR-TGF alpha, EGF), and DNA ploidy pattern, which is thought to be the result of an accumulation of genomic abnormalities are also prognostic factors for esophageal cancer.
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PMID:[Prognostic factors for esophageal cancer--from the viewpoint of molecular biology]. 868 32

Thirty-three esophageal tumors were analyzed by immunohistochemistry for P53 nuclear protein accumulation, and the results were compared to p53 gene mutations by PCR-direct sequence analysis. A highly significant correlation between the presence of p53 mutations and p53 nuclear protein accumulation was found. Of 33 tumors, 23 (69.7%) that demonstrated P53 protein expression 12(36%) had p53 mutations. Of 12 tumors with p53 mutations, 9 tumors showed P53 intensive nuclear reactivity. The results reported here are consistent with the idea that p53 mutations may be an important biological event in esophageal cancer progression and P53 expression was correlated with p53 gene mutation.
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PMID:[Correlation between p53 nuclear protein accumulation and mutations of the p53 gene in human esophageal cancer from linxian]. 869 89

A mutational spectrum for exons 5-8 of the p53 tumor suppressor gene in esophageal carcinomas in mainland China and Hong Kong was established. This study involved 209 squamous cell carcinoma specimens obtained from five different geographical locales in China: Zhengzhou, Taiyuan, Shantou, Guangzhou, and Hong Kong. Zhengzhou and Shantou were high-incidence regions for esophageal cancer, whereas the other three regions had low or intermediate incidence of the disease. Analysis by single-strand conformation polymorphism and DNA sequencing showed that 87 specimens (41.6%) contained mutations in exons 5-8 of the p53 gene compared to 163 cases (78%) that had accumulation or aberrant expression of the protein, as detected by immunohistochemical staining. Point mutations accounted for 80.4% (87/107) of all genetic changes. The specimens from northern China exhibited fewer p53 gene aberrations and a more even distribution of mutations in exons 5-8 compared to those from southern China in which 60% of all mutations were found in exon 5. A major hot spot was found at codon 176 in exon 5, where 41 samples from Shantou, Guangzhou, and Hong Kong had a G-->T transversion. It is likely that among southern Chinese this codon is susceptible to mutagenesis by carcinogens. Codons 175, 203, 245, 250, 273, and 282 were also shown to be mutational hot spots, with three or more mutations observed at each site. The p53 mutational data obtained in this study showed that Chinese esophageal carcinomas are often associated with some unique genetic alterations, which may be attributed to specific dietary or environmental carcinogens that affect the Chinese but not Caucasians.
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PMID:p53 mutational spectrum of esophageal carcinomas from five different geographical locales in China. 872 19

In the esophagus, alterations in the p53 tumor suppressor gene are associated with the development of preinvasive neoplastic lesions to invasive carcinoma. The role of p53 gene mutation in the progression of esophageal cancer still remains unclear. In this study, 82 DNA samples extracted from formalin-fixed, paraffin-embedded esophageal cancer tissues were analyzed for p53 mutation by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. All the patients had been treated surgically and were Japanese. Exons 5 through 8 of the p53 gene were amplified in DNAs and the mutations detected in 28 cases (34%) did not correlate with tumor location, histopathologic classification, histologic depth of tumor invasion, lymph node involvement or clinical stage. Among 39 patients with stage 3 and 4 disease who had undergone radical esophageal resection, those with p53 mutation had a poorer prognosis, the two-year survival being 25.4% compared with 61.2% for those without p53 mutation (P<0.01). These results suggest that p53 gene mutations play an important role not only in the genesis but also the progression of human esophageal cancer.
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PMID:Prognostic significance of the p53 mutation in esophageal cancer. 889 66

Serum antibodies reacting with the tumor suppressor protein p53 have been detected previously in cancer patients with a variety of neoplasms. Two initial (although insufficient) prerequisites for a B-cell response to occur have been proposed: p53 protein accumulation in the tumor or a mutant p53 gene, or both. We have examined 65 esophageal cancer cases (42 from Guangzhou and Shenyang, People's Republic of China, and 23 from Paris, France) to obtain a prevalence estimate of anti-p53 antibodies for this type of cancer and to define the relationship of p53 tumor status to B-cell immune response. Sera were analyzed in a triplicate assay (enzyme-linked immunoassay, immunoprecipitation, and immunoblot) for anti-p53 antibodies. Tumor DNA was screened for mutations in exons 5-8, and tumor tissue was examined by immunohistochemistry for abnormal p53 protein accumulation. p53 mutations were found in 36 (58%) of 62 cases analyzed. Sixteen patients (25%) had circulating antibodies to the tumor suppressor protein. All but two (88%) of the tumors from seropositive cases had a mutation in the DNA binding region of the p53 gene, and with one exception, these tumors also showed nuclear accumulation of the p53 protein. In contrast, tumor mutations were found in just 22 (46%) of the 48 individuals in whom we did not detect anti-p53 antibodies. Among the 22 seronegative cases for which we found no tumor mutations, 11 revealed p53 protein accumulation by immunohistochemical analysis. Thus, circulating anti-p53 antibodies may be present in one-fourth of esophageal cancer patients, most of whom also would be expected to have a p53 gene mutation in their tumors. Patients without such mutations appear considerably less likely to mount a B-cell response to the p53 tumor suppressor protein than those that do (P < 0.01).
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PMID:Circulating anti-p53 antibodies in esophageal cancer patients are found predominantly in individuals with p53 core domain mutations in their tumors. 889 44

We have identified a novel gene inducible by wild-type p53. A significant correlation between expression of this gene and p53 status in cells derived from esophageal cancers indicated that this gene is likely to be specifically regulated in a p53-dependent manner. As the predicted amino acid sequence showed a high degree of homology to the family of glycosyl-phosphatidylinositol (GPI)-anchored membrane proteins, we termed this gene GML (GPI-anchored molecule-like protein). Introduction of GML cDNA suppressed the growth of esophageal cancer cells in culture. A correlation between the presence of GML expression and the sensitivity of esophageal cancer cells to anti-cancer drugs implied that the gene product plays a significant role in the apoptotic pathway or cell-cycle regulation induced by p53 after DNA damage.
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PMID:Isolation of a novel GPI-anchored gene specifically regulated by p53; correlation between its expression and anti-cancer drug sensitivity. 893 43

The occurrence and the relevance in squamous cell carcinomas (SCC) and Barrett's adenocarcinomas (ADC) of genetic alterations, namely mutations in the p53 gene, allelic loss at various chromosomal loci and altered expression of genes involved in the regulation of cell proliferation, are described and discussed with reference to the etiology and pathogenesis of esophageal cancers. Mutations in the p53 gene occur in both SSC and ADC with a frequency of up to approximately 80%, although with a strikingly different pattern of mutations. In ADC, a very high frequency of G > A transitions at CpG dinucleotides was observed, whereas in SCC, mutations at A:T base pairs was comparatively high. In addition, in SCC, the frequency of p53 mutations was related to tobacco smoking. These data therefore indicated that such mutation analysis could provide valuable insight into the etiology of this cancer. It is also apparent that the genetic alterations involving genes other than p53 are also present in the natural history of esophageal cancer. The significance of these genetic changes as well as alterations of expression of cell cycle regulatory genes in esophageal carcinogenesis is briefly discussed.
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PMID:Molecular etiopathogenesis of esophageal cancers. 896 25

Alteration of the p53 gene is thought to be important in the early stages of human esophageal cancers, but how this confers a selective advantage to esophageal cancer cells is unknown. In this report, we analyzed 9 cell lines derived from human esophageal cancers (TE-1, TE-3, TE-6, TE-7, TE-9, TE-10, TE-11, TE-13 and TE-15) for mutations in the p53 sequence, p53 protein expression and p53 protein DNA-binding activity. The cell lines could be grouped in 3 categories, including (1) cell lines with mis-sense mutations in the coding sequence and accumulation of mutant proteins (TE-1, TE-6, TE-10 and TE-11); (2) cell lines expressing truncated forms of p53 as a result of frameshift (TE-9) or splice-site (TE-15) mutations; and (3) cell lines with wild-type p53 sequences but with impaired expression of p53 mRNA and protein, suggesting that p53 is inactivated by transcriptional repression (TE-3, TE-7 and TE-13). With the exception of TE-1, none of the cell lines exhibited p53-DNA-binding activity. In TE-1, a mutation at codon 272 (methionine to valine) generated a protein that retains basal DNA-binding activity, but that was not activated in response to DNA damage, suggesting that this mutation prevented p53 induction by genotoxic stress. Thus, p53 activity was impaired in all esophageal cell lines, including those containing wild-type p53 sequences.
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PMID:Inactivation of the p53 protein in cell lines derived from human esophageal cancers. 909 69

We investigated the p53 expression and the presence of HPV DNA in 90 patients with squamous cell carcinomas (SCCs) of the head and neck and the relation to clinicopathological parameters and patients' prognosis. Immunohistochemical analysis of p53 protein was conducted by using monoclonal anti-p53 antibody, clone 1801 and clone 240. The relationship between the overexpression of p53 and the duration of survival of patients was analyzed. The polymerase chain reaction (PCR) was carried out with consensus primers capable of detecting HPV16, 18, 31, 33, 52b and 58. In situ hybridization was performed in the mesopharyngeal carcinoma to confirm the presence of HPV genomes in cancer cells with a wide-spectrum cDNA probe capable of detecting HPV6, 11, 16, 18, 30, 31, 33, 35, 45, 51, 52. Forty-five tissue samples (50%) were immunohistochemically positive for p53. T-category, N-category, primary site of tumor, clinical stage and tumor differentiation did not correlate with p53 expression. Our finding that p53 overexpression occurred in 50% of head and neck tumor samples is similar to the frequency of p53 overexpression reported for both lung and esophageal cancer. The common risk factor is the same in these neoplasms, and therefore it is not surprising to find a similar percentage of p53 overexpression. The prevalence of metastasis was higher in the patients with p53-positive staining than in those with p53-negative staining (p < 0.10). Analysis of cumulative survival rates of patients by the Kaplan-Meier method showed a close correlation between p53 expression and survival time. The survival differences according to p53 immunostaining were significant (p 0.05). Our results indicate that p53 immunohistochemical evaluation may be useful as one of the new prognostic parameters in head and neck cancer patients. The HPV genomes were detected in 9 of 90 patients (10.0%); 8 of 9 patients with mesopharyngeal cancer and one with maxillary cancer, namely, 29.6% of mesopharyngeal cancers and 6.7% of maxillary cancer contained HPV DNA sequences. Seven of 8 patients had SCCs of tonsil origin. Almost all of the HPV infections in our study occurred in patients with mesopharyngeal cancer, and it has been suggested that this anatomic subsite may be more frequently infected by HPV than other sites within the head and neck region. Among the 27 patients with mesopharyngeal cancer, HPV DNA-positive patients experienced a higher incidence of complete remission than HPV DNA-negative patients (87.5% vs. 26.3%, p < 0.05).
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PMID:[Detection of human papilloma virus DNA and expression of p53 protein in patients with head and neck cancer]. 918 31


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