Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell kinetics: implication for gastric carcinogenesis.
BACKGROUND
Cyclooxygenase (COX)-2 induced by Helicobacter pylori is thought to enhance gastric carcinogenesis by affecting the maintenance of epithelial homeostasis.


METHODS
Gastric biopsies from 160 subjects, 97 with nonulcer dyspepsia (47 H. pylori negative, 50 H. pylori positive) and 63 with gastric cancer were examined immunohistochemically for COX-2 expression, cell proliferation and apoptotic indices.


RESULTS
COX-2 expression in corpus was significantly higher in H. pylori positive than in negative non-ulcer dyspepsia (NUD) (p <.05). Regardless of site, gastric cancer subjects had higher COX-2 expression in both antrum and corpus compared with H. pylori negative and positive NUD (p <.005). Proliferation was higher in cancer and H. pylori positive than in negative NUD (p <.0001). Moreover, cancer had enhanced proliferation than H. pylori positive NUD in corpus greater (p =.0454) and antrum lesser (p =.0215) curvatures. Apoptosis was higher in H. pylori positive than in negative NUD (p <.05). However, both had a higher index than the cancer subjects (p <.0001). Apoptosis : proliferation ratio was higher in corpus of H. pylori negative than in positive NUD in greater (p =.0122) and lesser (p =.0009) curvatures. However, both had a higher A:P ratio than cancer cases (p =.0001). A negative correlation between COX-2 expression and A:P ratio was found in corpus greater (r = -.176, p =.0437) and lesser (r = -.188, p =.0312) curvatures.


CONCLUSIONS
The expression of COX-2 is associated with disruption in gastric epithelial kinetics and hence may play a role in gastric carcinogenesis.
Wambura
Casmir
C
Second department of Internal medicine and Department of Endoscopy, Kobe University School of Medicine, Japan.
Aoyama
Nobuo
N
Shirasaka
Daisuke
D
Sakai
Toshiyuki
T
Ikemura
Takahiro
T
Sakashita
Masanori
M
Maekawa
Shuji
S
Kuroda
Kohei
K
Inoue
Takashi
T
Ebara
Shigeyuki
S
Miyamoto
Masaki
M
Kasuga
Masato
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002455:Cell Division; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D005260:Female; D016481:Helicobacter Infections / Q000201:enzymology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism*; D013270:Stomach / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology
D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases