Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the gastric pylorus.
BACKGROUND
Duodenogastric reflux after surgery increases the risk of gastric carcinoma. To determine whether bile reflux influences the development of gastric cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2) immunoreactivity in early gastric cancer originating from the gastric pylorus and that originating from other locations. We also examined the effects of bile acids on the expression and activity of COX-2 in gastric cells in vitro.


METHODS
Tumor sections from 79 patients who underwent endoscopic mucosal resection for early intestinal-type gastric carcinoma were stained using a COX-2-specific monoclonal antibody. Immunoblotting of COX-2 was used to assess the effects of bile acids on COX-2 expression and activity in human gastric cell lines.


RESULTS
Among the 79 early gastric cancer lesions studied, 13 (16%) arose in the gastric pylorus. In this group, COX-2 immunoreactivity was negative to weak in 38% (5 of 13 lesions) and moderate to strong in 62% (8 of 13 lesions). In the control group, COX-2 immunoreactivity was negative to weak in 70% (46 of 66 lesions) and moderate to strong in 30% (20 of 66 lesions). COX-2 expression was significantly elevated in early gastric cancer located in the gastric pylorus, compared with that in the other locations. In human gastric cell lines, bile acids induced COX-2 expression, mediated by the ERK 1/2 mitogen-activated protein kinase pathway.


CONCLUSIONS
COX-2 expression is elevated in early gastric cancer of the gastric pylorus, a common site of gastric cancer. Bile acids induced COX-2 expression in human gastric cell lines, suggesting a role of bile reflux in gastric carcinogenesis.
Yasuda
Hiroshi
H
Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama, 227-8501, Japan.
Yamada
Masaya
M
Endo
Yutaka
Y
Inoue
Kazuaki
K
Yoshiba
Makoto
M
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011708:Pylorus / Q000473:pathology*; D012189:Retrospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases