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

Abstract

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.

Expression of mutant type-p53 products inH pylori-associated chronic gastritis

“…[32] demonstrated that the expression of p53 and apoptotic indices in gastritis in the absence of intestinal metaplasia are significantly higher in H pyloripositive patients than in H pylori-negative patients. These studies are in agreement with our results indicating that in some p53 mutations are found mutant type-p53 products in the H pylori-infected gastric pits.…”

“…Our results indicated that while the majority of cells that reacted with p53 (DO-7) account for an accumulation of wild-type p53, mutant type p53 might also be expressed in some cells of the gastric pit. Murakami et al [14] and Morgan et al [31] reported the presence of point mutations in exon 5 to 8 of p53 in H pylori-positive gastritis, and several other studies have shown that gastric precancerous lesions, such as atrophic gastritis and intestinal metaplasia, are associated with p53 abnormalities [20][21][22]26,32] . Murakami et al [14] reported that the point mutations are present in 52.4% of the gastritis, with Morgan et al [31] reporting the presence of p53 mutations in 35% of the gastritis and 45% of the intestinal Figure 2 Labeling indices for p53 (DO-7) in 42 patients with H pylori infection, 6 mo after eradication, and 11 patients without H pylori infection.…”

“…Nardone et al [26] reported that DNA aneuploidy was seen in 11 patients with H pylori infection and atrophy, with 8 of these found to show c-Myc expression, and 6 of these to have p53 expression, and they concluded that chronic H pylori infection may be responsible for genomic instability in a subset of H pylori-positive chronic atrophic gastritis. Unger et al [32] also reported that H pylori-positive gastritis accompanied with intestinal metaplasia showed a lack of increased apoptosis with a higher p53 expression, which suggests an increased genetic instability, thus concluding that p53 mutation is an early step in the multi-step process of gastric carcinogenesis. Our results confirm the relationship between atrophic and/or metaplastic gastric mucosa with H pylori infection and genetic instability, which lead to gastric carcinogenesis.…”

New Aspects of Helicobacter pylori Infection Involvement in Gastric Oncogenesis

“…frequent in gastric cancer. In addition, p53 mutations are also observed in intestinal metaplasia (38%) and gastric dysplasia (58%), suggesting that mutations of the p53 gene may be an early event and perhaps work together with RAS oncogene in the pathogenesis of gastric cancer [9]. Further evidence for a role of p53 in the early stages of gastric cancer development comes from studies in mice that are hemizygous for p53, which display an increased proliferative response to H. pylori infection compared with wild-type mice.…”

“…The best studied and most common oncogene alteration in colonic neoplasm involves the RAS oncogene, which also works together with p53 gene mutation in gastric carcinogenesis [9] and up-regulates the gene expression of gastrin. The latter is an oncogenic growth factor contributing to gastric and colon carcinogenesis [6,19].…”