Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia

Zsuzsa Unger, B. Molnár, L. Prónai, Erika Szaleczky, T. Zágoni, Z. Tulassay

Research output: Article

26 Citations (Scopus)

Abstract

Background: Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. Methods: Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. Results: In the absence of intestinal metaplasia, both the apoptotic index (0.0272 ± 0.011 vs 0.0128 ± 0.006) and expresssion of p53 (35.55 ± 31.16 vs 18.33 ± 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P <0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 ± 0.004 vs 0.011 ± 0.004), or p53 ratio (70.16 ± 22.54 vs 68.50 ± 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P <0.05). Conclusion: In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.

Original languageEnglish
Pages (from-to)389-393
Number of pages5
JournalEuropean Journal of Gastroenterology and Hepatology
Volume15
Issue number4
DOIs
Publication statusPublished - ápr. 1 2003

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Metaplasia
Gastritis
Helicobacter pylori
Helicobacter Infections
Tumor Suppressor Protein p53
Apoptosis
Stomach
p53 Genes
Carcinogenesis
Epithelium
Biopsy
Mutation
Transferases
Gastric Mucosa
Paraffin
Formaldehyde
Endoscopy
Stomach Neoplasms
Homeostasis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{564131b4313142208ef40fd3d1dc816c,
title = "Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia",
abstract = "Background: Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. Methods: Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. Results: In the absence of intestinal metaplasia, both the apoptotic index (0.0272 ± 0.011 vs 0.0128 ± 0.006) and expresssion of p53 (35.55 ± 31.16 vs 18.33 ± 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P <0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 ± 0.004 vs 0.011 ± 0.004), or p53 ratio (70.16 ± 22.54 vs 68.50 ± 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P <0.05). Conclusion: In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.",
keywords = "Apoptosis, Helicobacter pylori infection, Intestinal metaplasia, p53 oncoprotein",
author = "Zsuzsa Unger and B. Moln{\'a}r and L. Pr{\'o}nai and Erika Szaleczky and T. Z{\'a}goni and Z. Tulassay",
year = "2003",
month = "4",
day = "1",
doi = "10.1097/00042737-200304000-00009",
language = "English",
volume = "15",
pages = "389--393",
journal = "European Journal of Gastroenterology and Hepatology",
issn = "0954-691X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia

AU - Unger, Zsuzsa

AU - Molnár, B.

AU - Prónai, L.

AU - Szaleczky, Erika

AU - Zágoni, T.

AU - Tulassay, Z.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Background: Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. Methods: Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. Results: In the absence of intestinal metaplasia, both the apoptotic index (0.0272 ± 0.011 vs 0.0128 ± 0.006) and expresssion of p53 (35.55 ± 31.16 vs 18.33 ± 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P <0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 ± 0.004 vs 0.011 ± 0.004), or p53 ratio (70.16 ± 22.54 vs 68.50 ± 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P <0.05). Conclusion: In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.

AB - Background: Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. Methods: Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. Results: In the absence of intestinal metaplasia, both the apoptotic index (0.0272 ± 0.011 vs 0.0128 ± 0.006) and expresssion of p53 (35.55 ± 31.16 vs 18.33 ± 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P <0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 ± 0.004 vs 0.011 ± 0.004), or p53 ratio (70.16 ± 22.54 vs 68.50 ± 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P <0.05). Conclusion: In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.

KW - Apoptosis

KW - Helicobacter pylori infection

KW - Intestinal metaplasia

KW - p53 oncoprotein

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JO - European Journal of Gastroenterology and Hepatology

JF - European Journal of Gastroenterology and Hepatology

SN - 0954-691X

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