Enhanced cellular proliferation and p53 accumulation in gastric mucosa chronically infected with Helicobacter pylori.
This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.
Hibi
K
K
Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Mitomi
H
H
Koizumi
W
W
Tanabe
S
S
Saigenji
K
K
Okayasu
I
I
D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D002455:Cell Division; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D010435:Pepsinogens / Q000097:blood; D010437:Peptic Ulcer / Q000378:metabolism / Q000382:microbiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014510:Urease / Q000032:analysis
D000907:Antibodies, Bacterial; D019394:Ki-67 Antigen; D010435:Pepsinogens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014510:Urease