Cyclooxygenase-2 expression in human gastric tubular adenomas and carcinomas; correlation with intratumoral microvessel density and apoptotic index.
BACKGROUND
Cyclooxygenase (COX)-2 plays an important role in carcinogenesis in various human malignancies. This study examined the relationship among COX-2 expression, angiogenesis and apoptosis in human gastric adenoma and carcinoma.


METHODS
We examined the expression of COX-2 in 30 tubular adenomas and 11 carcinomas, comparing it with intratumoral microvessel density (IMVD) and apoptotic index (AI) by immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxygenin nick-end labeling (TUNEL) procedure.


RESULTS
Immunohistochemistry demonstrated positive expression of COX-2 in 15 (50.0%) adenomas and in 50 (53.1%) carcinomas, respectively. The frequency of COX-2 expression was significantly higher in intestinal-type carcinomas than in diffuse-type, regardless of the tumor stage. The IMVD was significantly higher in the early and advanced carcinomas than in the adenomas and also higher in the COX-2-positive adenomas and carcinomas than in the negative ones. The AI was significantly higher in the adenomas than in the carcinomas and also in the COX-2-negative adenomas and intestinal-type early carcinomas than in their positive counterparts, respectively (p < 0.05). The IMVD and AI showed significant inverse correlation in both the adenomas (p=0.02, r=-0.64) and carcinomas (p=0.04, r=-0.18).


CONCLUSIONS
COX-2 expression might be an early event in gastric tumorigenesis and provide a preferential advantage for tumor cell proliferation because of its vascular-rich microenvironment and escape from tumor cell apoptosis, especially in intestinal-type gastric carcinomas.
Honjo
Soichiro
S
Division of Organ Pathology, Department of Microbiology and Pathology and Faculty of Medicine, Tottori University, Yonago, Tottori, 683-8503, Japan. honjo@grape.med.tottori-u.ac.jp
Kase
Satoru
S
Osaki
Mitsuhiko
M
Ardyanto
Tonang Dwi
TD
Kaibara
Nobuaki
N
Ito
Hisao
H
D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D000236:Adenoma / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D051546:Cyclooxygenase 2; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases