Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue.
In vitro studies suggest that cyclooxygenase-2 (COX-2) induces angiogenesis by stimulating angiogenic growth factors while inhibiting apoptosis in cancer cell lines. A series of 107 gastric adenocarcinoma cases that had undergone gastrectomy was studied to determine the correlation between COX-2 expression, angiogenesis, and apoptosis in human gastric cancer tissue. COX-2, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and Bcl-2 were stained by single and dual immunoassaying methods. Microvessel density was determined by immunostaining for CD34. Apoptosis was evaluated with the TUNEL assay. COX-2 expression was positive exclusively in cancer cells in 46 cases (43%). COX-2 expression significantly correlated with VEGF and PDGF expression. Dual staining for COX-2 and VEGF showed that colocalization of these proteins was most frequent at the advancing edge of cancer cells. Microvessel density was higher in COX-2-and VEGF-positive cases than in COX-2- and VEGF-negative cases. In addition, COX-2 expression correlated with Bcl-2 expression. The apoptotic index was lower in COX-2-positive cancer cells than in COX-2-negative cases. Multivariate analysis revealed that coexpression of COX-2 and VEGF, age, lymph node status, and serosal invasion were independent prognostic factors for overall survival in gastric cancer patients. Therefore, these data suggest that COX-2 contributes to gastric cancer development by promoting angiogenesis and inhibiting apoptosis.
Tatsuguchi
Atsushi
A
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Matsui
Kazuhiro
K
Shinji
Yoko
Y
Gudis
Katya
K
Tsukui
Taku
T
Kishida
Teruyuki
T
Fukuda
Yuh
Y
Sugisaki
Yuichi
Y
Tokunaga
Akira
A
Tajiri
Takashi
T
Sakamoto
Choitsu
C
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000096:biosynthesis*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D018613:Microscopy, Confocal; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018952:Antigens, CD34; D007527:Isoenzymes; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases