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


CONCLUSIONS
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.
Kodama
Masaaki
M
Department of Gastroenterology, Oita University, Hasama-machi, Oita, 879-5593, Japan. kodm@med.oita-u.ac.jp
Murakami
Kazunari
K
Okimoto
Tadayoshi
T
Sato
Ryugo
R
Watanabe
Koichiro
K
Fujioka
Toshio
T
D000368:Aged; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D005786:Gene Expression Regulation; D042822:Genomic Instability; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D013274:Stomach Neoplasms / Q000517:prevention & control; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53