Compartment theory in Helicobacter pylori-associated gastric carcinogenesis.
BACKGROUND
The compartment theory has not been well investigated in gastric carcinogenesis. This study was aimed at examining the compartment alterations through the Helicobacter pylori (H. pylori)-related chronic gastritis-intestinal metaplasia-carcinoma sequence, and investigating the long-term effect of bacterial eradication on the compartment changes.


METHODS
Gastric biopsy specimens were obtained from subjects with H. pylori-negative normal mucosa (N = 12), H. pylori-positive non-metaplastic gastritis (N = 42), H. pylori-positive intestinal metaplasia (N = 21) and intestinal-type adenocarcinoma (N = 20). The specimens were immnostained for monocloncal antibodies against the proliferating cell nuclear antigen (PCNA) for proliferating analysis. Additionally, 50 patients with H. pylori-positive gastritis were enrolled to investigate the long-term effect of bacterial eradication on the compartment changes of gastric epithelium.


RESULTS
The mean PCNA labeling indices (L.I.) of non-metaplastic gastritis, intestinal metaplasia and adenocarcinoma were significantly higher than that of normal mucosa (31.1, 49.2 and 40.7 vs. 21.4; p < 0.01, 0.001 and 0.001, respectively). The proliferating zone was principally located in the lower compartment of normal mucosa. In patients with intestinal metaplasia, there was a full expansion (phase 1 change) of proliferating zone to the middle compartment of gastric pits (ratio of L.I. between middle and lower compartment = 1.00). The proliferating cells were evenly distributed in adenocarcinoma (complete loss of compartmentalization). Eradiation of H. pylori led to a reversion of compartment changes of gastric epithelium in patients with chronic gastritis.


CONCLUSIONS
H. pylori-related gastric carcinogenesis is a multistep process involving progressive alterations of proliferating activity as well as loss of compartmentalization. Eradication of H. pylori reverses the changes in growth kinetics of gastric epithelium.
Tseng
Hui-Hwa
HH
Department of Pathology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taipei, Taiwan, R.O.C.
Hsu
Ping-I
PI
Chen
Hui-Chun
HC
Lai
Kwok-Hung
KH
Lo
Gin-Ho
GH
Lo
Ching-Chu
CC
Chou
Nan-Hua
NH
Mok
King-Tong
KT
Chen
I-Shu
IS
Chou
Nan-Haw
NH
Yang
Hsiao-Bai
HB
Liu
Les
L
Hsu
Ping-Ning
PN
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000230:Adenocarcinoma / Q000382:microbiology* / Q000473:pathology; D000368:Aged; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002908:Chronic Disease; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications* / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008679:Metaplasia / Q000382:microbiology / Q000473:pathology; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology; D013752:Tetracycline / Q000627:therapeutic use
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064747:Lansoprazole; D008795:Metronidazole; D013752:Tetracycline; D009853:Omeprazole