Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia.
BACKGROUND
The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the detection of apoptotic cells in tissue sections has facilitated the analysis of the role of apoptosis in the gastritis-atrophy-intestinal metaplasia sequence.


METHODS
Archival material from 40 gastric resection specimens with normal mucosa (n = 5), chronic active gastritis (n = 17), or intestinal metaplasia (n = 18) was studied. Immunohistochemistry was performed using antibodies directed against cleaved cytokeratin 18 and active caspase 3. Slides were scored on a 0-3 scale for the presence of apoptotic cells.


RESULTS
Normal gastric mucosa contained low numbers of apoptotic cells at the surface epithelium (mean score, 0.20). This number was significantly increased in cases with chronic gastritis (mean score, 1.06) and in those with intestinal metaplasia (mean score, 2.56). Within the intestinal metaplasia cases, 44 different foci of intestinal metaplasia were identified. In 39 of these 44 areas, concentrations of apoptotic cells were seen immediately adjacent to the foci of intestinal metaplasia, but not in the metaplastic epithelium itself.


CONCLUSIONS
Apoptosis is uncommon in normal gastric mucosa. Chronic inflammation and intestinal metaplasia are associated with increased apoptosis, but occur mainly at the mucosal surface and not in the deeper layers. These findings do not support the concept that apoptosis underlies the loss of gastric glands and leads to atrophy, but the observed concentration of apoptotic epithelial cells adjacent to foci of intestinal metaplasia could be related to heterogeneity of epithelial damage, causing apoptosis, to which intestinal metaplasia is a response.
Department of Gastroenterology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
N C T
NC
van Grieken
G A
GA
Meijer
A
A
zur Hausen
S G M
SG
Meuwissen
J P A
JP
Baak
E J
EJ
Kuipers
D017209:Apoptosis; D002908:Chronic Disease; D018450:Disease Progression; D005753:Gastric Mucosa / Q000473:pathology*; D005756:Gastritis / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008679:Metaplasia; D011230:Precancerous Conditions / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*