p16Ink4a is overexpressed in H. pylori-associated gastritis and is correlated with increased epithelial apoptosis.
BACKGROUND
Cell cycle regulatory proteins may be critical targets during carcinogenesis. We have previously shown that chronic H. pylori infection is associated with decreased expression of the cyclin dependent kinase inhibitor (CDI) p27kip1. Loss of p27kip1 and p16Ink4a (p16) expression, another CDI, has been reported during the progression of gastric tubular adenomas to advanced gastric cancer. The aim of the current study was to examine whether H. pylori infection also affects the expression of p16 in the gastric mucosa of H. pylori-infected patients.


METHODS
p16 expression was evaluated in gastric antral biopsies by immunohistochemistry in 50 patients with nonulcer dyspepsia (n = 18 uninfected, n = 32 H. pylori infected, 24 by cagA+ strains). Adjacent sections were stained for proliferating epithelial cells (by Ki67) and for apoptotic cells (by TUNEL assay).


RESULTS
Both in H. pylori infected and uninfected patients the expression of p16 was higher in the neck and base of the gland than in the foveolar region. Epithelial staining for p16 was increased with H. pylori infection (31.3% vs. 11.1% in the foveolar region, 68.8% vs. 27.8% in the neck and 75% vs. 50% in the glandular base). There was no correlation between the expression of 16 and proliferation but there was a significant positive correlation between apoptosis and 16 immunostaining.


CONCLUSIONS
The tumor suppressor gene 16 is over expressed in gastric epithelial cells of H. pylori infected patients and this is associated with an increase in apoptosis. These findings suggest a possible role for this cell cycle regulator in the increase in gastric cell turnover that is associated with H. pylori infection.
Shirin
Haim
H
Department of Gastroenterology, The E. Wolfson Medical Center, Sackler Faculty of Medicine, TelAviv University, Israel.
Hibshoosh
Hanina
H
Kawabata
Yuichi
Y
Weinstein
I Bernard
IB
Moss
Steven F
SF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002453:Cell Cycle; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000209:etiology
D019941:Cyclin-Dependent Kinase Inhibitor p16