Gastric carcinogenesis has been studied in various aspects. Helicobacter pylori (Hp) infection and mutation of the p53 tumor suppressor gene have recently been argued to be important factors of gastric carcinogenesis. There have been many studies to determine the precise mechanism of how Hp is related to gastric cancer, but it is so far still unknown. We studied the relationship of Hp infection and p53 overexpression and tried to discover some significance in clinicopathologic factors such as age, sex, stage, site, differentiation and gross morphology. Ninety-six patients who were diagnosed with gastric cancer at Severance Hospital, Yonsei University Medical College from November 1995 to March 1996, and 96 control patients of non-ulcer dyspepsia (NUD) were studied by endoscopic biopsy of normal gastric tissue and cancer tissue. They also underwent the CLO (Delta West, Melbourne, Western Australia) test for Hp positivity and p53 immunohistochemical stain for p53 positivity. These data were analyzed for comparison with the clinicopathologic characteristics of gastric cancers. In conclusion, the differentiated group cancer had a significantly high Hp positivity and p53 positivity. There is a possibility that Hp infection and p53 tumor suppressor gene mutation might be significantly related in the gastric carcinogenic process of well- and moderately-differentiated adenocarcinomas, but further study is necessary to determine more direct clues on the carcinogenic roles of these factors.
Adenocarcinoma/metabolism* ; Adult ; Aged ; Female ; Helicobacter Infections/metabolism* ; Helicobacter pylori* ; Human ; Male ; Middle Age ; Protein p53/analysis* ; Stomach Neoplasms/metabolism*

Endoscopic mucosal resection (EMR) has been standardized for the treatment of intestinal type of intramucosal gastric carcinomas, and careful histological examination of the resected specimen is important for further treatment. To evaluate the diagnostic utility of p53 expression in gastric EMR samples, using immunohistochemical staining, we examined 24 gastric carcinomas (22 intestinal types and two diffuse types) and 20 adenomas removed by EMR. Intestinal type of adenocarcinomas revealed strong p53 expression in 13 cases (59%), weak in four cases (18%), and negative in five cases (23%). Resection margins of 11 carcinomas were involved in the carcinoma cells, which showed the same p53 expression pattern with main carcinoma cells. Squeezed carcinoma cells, remaining in resection margins, were definitely identified by strong p53 expression in seven cases of which the main tumor strongly expressed p53. Microscopic in situ carcinoma could be easily detected in p53 immunostaining. Multifocal involvement and submucosal invasion of carcinomas could be demarcated easily and definitely by strong p53 expression of carcinoma cells. All adenomas showed diffuse weak p53 expression. The difference of p53 expression (p< 0.001) could be used as a differential diagnosis between adenomas and carcinomas. According to these results, we propose that for careful histological examination in hospital diagnosis, both histological evaluation and p53 immunostaining are important diagnostic parameters in EMR samples of the intestinal type of gastric carcinomas.
Adenocarcinoma/surgery ; Adenocarcinoma/pathology ; Adenoma/surgery* ; Adenoma/pathology* ; Endoscopy* ; Gastric Mucosa/metabolism ; Gastric Mucosa/chemistry ; Human ; Immunoenzyme Techniques ; Protein p53/diagnostic use* ; Protein p53/biosynthesis ; Protein p53/analysis ; Stomach Neoplasms/surgery* ; Stomach Neoplasms/pathology* ; Tumor Markers, Biological

BACKGROUND: Cyclin-dependent kinase inhibitors (CDKI), including p21, p27 and p57 of the KIP family, are negative regulators of cell cycle progression and potentially act as tumor suppressors. The expression of p21 is induced by tumor suppressor gene p53. Mutations of p53 are common and found in various human cancers. Thus, the function of p21 as a tumor suppressor may be not retained after p53 mutation in human cancers. The aim of our study was to evaluate the tumor suppressive activity of p21 and p53 in human gastric cancer. METHODS: One hundred and two patients who underwent surgery for gastric cancer at Chonnam National University Hospital were selected retrospectively for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of p21 and p53 in human gastric cancer tissue by immunohisto-chemistry and the correlation between their expression and clinicopathological variables. RESULTS: p21 and p53 immunoreactivities were localized in the nuclei of carcinoma cells. Positive nuclear expression of p21 and p53 was demonstrated in 63.7 and 33.3% of cancer tissues, respectively. No apparent correlation was noted between p21 and p53 expression. Negative expression of p21 correlated with advanced stage and lymph node metastasis (p=0.028 and 0.017, respectively). Moreover, negative expression of p21 correlated with poor survival (p=0.037). Positive expression of p53 correlated with depth of tumor invasion (p=0.029). However, no significant correlation could be observed between the status of p53 expression and survival. Combined analysis of p21 and p53 status showed that p21 negative and p53 positive tumors had a poorer survival than other group tumors (p=0.026). CONCLUSION: These results suggest that the status of p21 and p53 expression may help in predicting the aggressive behavior of gastric cancer. However, further studies are warranted to clarify the impact of p53 on the function of p21 as a tumor suppressor.
Adult ; Aged ; Carcinoma/genetics/*metabolism ; Female ; Gene Expression ; Genes, p53 ; Human ; Male ; Middle Aged ; Oncogene Protein p21 (ras) /genetics/*metabolism ; Prognosis ; Protein p53/genetics/*metabolism ; Retrospective Studies ; Stomach Neoplasms/genetics/*metabolism ; Survival Analysis ; Tumor Markers, Biological/genetics/*metabolism

According to the current concept of carcinogenesis, the alterations of p53 tumor suppressor gene have been the most frequently detected in both human cancer cell lines and cancer tissues freshly isolated. This study was conducted to investigate the p53 gene alteration in malignant melanoma. Nineteen tumor tissues were obtained from 19 patients with malignant melanoma and examined for the expression of p53 protein by immunohistochemical staining with mouse monoclonal anti-p53 antibody, NCL-p53-DO-7. Twelve out of 19 cases (63%) showed positive reactions for p53 protein: 26, 21 and 16% of which had low, intermediate and high reactivity, respectively. p53 alteration more frequently expressed in female (10/12) than male patients (2/7) with malignant melanoma (p<0.05). The incidence of expression of p53 protein was compared according to the stages and the sites of tissue obtained. The positive rate for p53 protein was not significantly different between the stages. The positive rates for p53 protein were five out of five (100%), one out of two (50%) and six out of twelve (50%) in tissues obtained from the metastatic, lymph node, and primary sites, respectively. The difference in the positive rates, however, is not statistically significant. These results suggest that p53 gene is a frequent target for mutation in the development of malignant melanoma.
Adult ; Aged ; Aged, 80 and over ; Female ; Genes, p53 ; Human ; Immunohistochemistry ; Male ; Melanoma/genetics/*metabolism ; Middle Age ; Protein p53/*analysis ; Sex Factors ; Support, Non-U.S. Gov't

OBJECTIVETo investigate the relationship between apoptosis-related proteins in gastric mucosa, p53 and Bax, and Helicobacter pylori (H. pylori) infection in children.

METHODSp53 and Bax expression in gastric mucosa were measured using immunohistochemical technique in 33 children with gastric mucosal lesions. Presence/absence of H. pylori infection was detected by the rapid urease and pathological tests.

RESULTSFifteen children (88%) showed positive expression of p53 in 17 children who were confirmed with H. pylori infection, compared with 9 (56%) in 16 H. pylori negative children. Thirteen children (76%) showed positive expression of Bax in the 17 children with H. pylori infection, compared with 6 (38%) in the 16 H. pylori negative children. The expression levels of p53 and Bax in the H. pylori positive group were significantly higher than those in the H. pylori negative group (p<0.05).

CONCLUSIONSH. pylori infection is associated with the over-expression of p53 and Bax proteins in gastric mucosa in children.

Child ; Female ; Gastric Mucosa ; chemistry ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Humans ; Immunohistochemistry ; Male ; Tumor Suppressor Protein p53 ; analysis ; bcl-2-Associated X Protein ; analysis

Recent molecular studies indicate two different genetic pathways leading to the development of glioblastoma; final progression of astrocytoma and de novo formation. To define the mutual relationships of cytogenetic changes in the pathogenesis of glioblastoma, molecular histopathologic alterations of p53 and epidermal growth factor receptor (EGFR) were evaluated by single stranded conformational polymorphion, reverse transcriptase-polymerase chain reaction and immunohistochemical stains in 15 primary and 21 secondary glioblastomas. Mutations in p53 gene and positive immunoreactivity to p53 protein (DO1) were more prevalent in secondary glioblastomas than in primary glioblastomas. A correlation between p53 mutations and p53 immunopositivities in glioblastomas was observed in 83.3% of the cases. All cases with positive p53 immunoreactivities showed p53 mutations; however, 13.9% of glioblastomas with p53 immuno-positivities lacked the relevant mutations. EGFR amplifications were detected in 73.3% of primary glioblastomas and 9.5% of secondary glioblastomas (p<0.001). The concurrence of p53 mutation and EGFR amplification was revealed in only 2 out of 15 primary glioblastomas and none among the secondary glioblastomas. Immunoreactivities for EGFR were noted in 66.7% of primary glioblastomas and in 9.5% of secondary glioblastomas (p<0.001). A correlation between EGFR amplification and EGFR immunopositivity in glioblastomas was observed in 91.7% of the cases. These data indicate that EGFR amplification and p53 mutations are two independent genetic events in the development of glioblastomas.
Adolescence ; Adult ; Brain Neoplasms/*genetics/metabolism ; Female ; *Genes, p53 ; Glioblastoma/*genetics/metabolism ; Human ; Immunohistochemistry ; Loss of Heterozygosity ; Male ; Middle Age ; *Mutation ; Protein p53/analysis ; Receptor, Epidermal Growth Factor/analysis/*genetics ; Reverse Transcriptase Polymerase Chain Reaction

Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Tissue Array Analysis ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo study the etiological clues involved (in esophageal cancer in Linzhou, Henan, a high-incidence area for esophageal cancer) by analyzing p53 mutational spectrum from esophageal precancerous and cancerous lesions.

METHODSUsing bolt bioinformatic and Monte Carlo methods to analyze p53 mutation spectra from "The IARC Database of Somatic p53 Mutations in Human Tumors and Cell Lines", "p53 Database at Institute Curic" and to establish a local database based on these data using the FileMark Pro 3.0 software to allow fast and off-line analysis on a PC from the authors' laboratory.

RESULTSWe found that esophageal squamous cell carcinomas from Linzhou had a lower prevalence of base substitutions associated with strand bias than those from other areas (32.8% vs 39.8%). However, a higher prevalence of G:C-->A:T transitions at CpG site (29.6% vs16.4%) was found. Esophageal squamous cell carcinomas from Linzhou displayed a distinctive profile of mutation hotspots, including codons 273 (covers 11.3% of all missense mutations), 175 (9.7%), 158 (9.7%), 159 (6.5%) and 282 (6.5%), all of which were at the CpG site. Statistical analysis showed that the p53 mutation profiles between esophageal squamous cell carcinomas from Linzhou and those from other areas were different (P = 0.02). The p53 mutation profiles of esophageal squamous cell carcinomas from Linzhou and from other areas were also different from cancer of the head and neck.

CONCLUSIONData showed that the p53 mutational spectrum of esophageal squamous cell carcinomas from Linzhou baring the characteristics of those caused both by endogenous and exogenous mutagenic agents, suggesting the potential involvement of chronic inflammation, unique dietary habits and carcinogen exposure in the pathogenesis of esophageal squamous cell carcinoma in Linzhou.

Carcinogens, Environmental ; toxicity ; Carcinoma, Squamous Cell ; epidemiology ; etiology ; genetics ; China ; epidemiology ; DNA Mutational Analysis ; Esophageal Neoplasms ; epidemiology ; etiology ; genetics ; Feeding Behavior ; Female ; Genes, p53 ; genetics ; Humans ; Male ; Point Mutation ; Precancerous Conditions ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

BACKGROUND/AIMS: Beta-catenin is known to perform two unrelated functions in cadherin-mediated cell to cell adhesion system and Wnt pathway. Recent studies reported cytoplasmic and nuclear accumulation of beta-catenin by Wnt signaling and/or abnormal Wnt pathway in cancer cells. Nuclear accumulations of beta-catenin have a crucial role in early tumor growth and initiation of invasive growth in gastric cancer. METHODS: We carried out clinicopathological and immunohistochemical studies for beta-catenin, p53, E-cadherin, and Ki-67 in the specimens from 60 early gastric cancer patients who were treated with curative resections. RESULTS: Twenty-five (41.7%) and twenty-nine (48.3%) cases showed a nuclear and cytoplasmic expression of beta-catenin, respectively. There were significant correlations between nuclear expression of beta-catenin and well-differentiated and intestinal type of early gastric carcinoma. Cytoplasmic expression of beta-catenin had significant correlations with nuclear expression of beta-catenin (p=0.011). CONCLUSIONS: Nuclear expression of beta-catenin is significantly influenced by histological grade, Lauren classification and cytoplasmic expression of beta-catenin in early gastric cancer. These findings suggest that nuclear expression of beta-catenin is correlated with early tumorigenesis and initiation of invasive growth in gastric cancer.
Adult ; Aged ; Aged, 80 and over ; Cadherins/*metabolism ; Carcinoma/*metabolism/pathology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Cytoskeletal Proteins/*metabolism ; English Abstract ; Female ; Humans ; Ki-67 Antigen/analysis ; Male ; Middle Aged ; Protein p53/metabolism ; Stomach Neoplasms/*metabolism/pathology ; Trans-Activators/*metabolism

OBJECTIVETo study the effect of hyperoxia exposure on the expression of p53 and proliferating cell nuclear antigen (PCNA) in fetal rat lung fibroblasts (LFs).

METHODSPrimary rat embryonic LFs were cultured in vitro. LFs grew to subconfluence and then were randomly divided into air and hyperoxia exposure (95% O₂, 5% CO₂) groups. After LFs were cultured for 12 and 24 hours, the proliferation was analyzed by MTT. p53 mRNA level was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). p53 and PCNA protein levels were determined by Western blot.

RESULTSAfter 12 and 24 hours of culture the growth inhibition rate of LFs was 8% and 23% respectively in the hyperoxia exposure group. p53 mRNA and protein levels increased significantly (P<0.01) in the hyperoxia exposure group after 12 and 24 hours of culture compared with the air exposure group. Hyperoxia exposure decreased PCNA expression after 24 hours of culture (P<0.01).

CONCLUSIONSHyperoxia exposure increases p53 level and decreases PCNA expression, resulting in inhibitions of LFs proliferation and DNA repair.

Animals ; Cell Proliferation ; Female ; Fibroblasts ; metabolism ; Hyperoxia ; metabolism ; pathology ; Lung ; cytology ; metabolism ; Proliferating Cell Nuclear Antigen ; analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tumor Suppressor Protein p53 ; analysis ; genetics