Expression of mutant type-p53 products in H pylori-associated chronic gastritis

Abstract

Aim: To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and after H pylori eradication therapy.

Methods: 53 subjects (36 male, 17 female, mean age +/- SEM, 57.1 +/- 12.1) undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylori-negative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 (DO-7 and PAb240).

Results: p53 (DO-7 and PAb240) immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 (PAb240) in the H pylori-infected gastric mucosa. The proportion of patients immunopositive for p53 (PAb240) was significantly reduced 6 mo after eradication [28/42 (66.7%) to 6/42 (14.3%)] (P < 0.05), while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 (PAb240). p53 (PAb240)-positive patients were divided into two groups by the number of positive cells detected: one with more than six positive cells per 10 gastric pits (group A, n = 12), and the other with less than five positive cells per 10 gastric pits (group B, n = 30). Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum (group A: 2.00 +/- 0.14 vs group B: 1.40 +/- 0.15, P = 0.012), the lesser curvature of the corpus (group A: 2.00 +/- 0.21 vs group B: 1.07 +/- 0.23, P = 0.017), and the greater curvature of the corpus (group A: 1.20 +/- 0.30 vs group B: 0.47 +/- 0.21, P = 0.031). Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum (group A: 2.10 +/- 0.41 vs group B: 1.12 +/- 0.29, P = 0.035).

Conclusion: H pylori-associated chronic gastritis expressed the mutant-type p53, which was significantly associated with more severe atrophic and metaplastic changes. H pylori eradication led to a significant reduction in the expression of the mutant-type p53. It is considered that H pylori-infected chronic gastritis is associated with a genetic instability that leads to gastric carcinogenesis, and H pylori eradication may prevent gastric cancer.

Figure 1

Immunohistochemistry for p53 (DO-7) in H pylori-infected gastric mucosa. Positive staining for p53 (DO-7) was observed in the gastric pit, especially in the neck region before eradication (× 200).

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. Results were shown as mean ± SEM. p53 (DO-7) indices were significantly reduced 6 mo after eradication at all biopsy sites. p53 indices for the H pylori-infected mucosa were significantly higher than those for the gastric mucosa without H pylori infection at all biopsy sites. ^bP < 0.001, vs H pylori non infected group.

Figure 3

Immunohistochemistry for p53 (PAb240) in the H pylori-infected gastric mucosa. A small number of cells clearly showing the expression of p53 (PAb240) were detected in the neck region before eradication. A: a 53-yr-old male with gastric ulcer; B: a 51-yr-old male with chronic gastritis; × 400).

Figure 4

Labeling indices for p53 (DO-7) in group A with more than 6 positive cells for p53 (PAb240) per 10 gastric pits (n = 12) and group B with less than 5 positive cells for p53 (PAb240) per 10 gastric pits (n = 30) before eradication. Results are shown as mean ± SEM. Labeling indices for p53 (DO-7) were significantly higher for group A than for group B at all biopsy sites except for the lesser curvature of the antrum. ^aP < 0.05, ^bP < 0.01, NS, not statistical.