Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival.
OBJECTIVE
Cyclo-oxygenase-2 seems to be involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between cyclo-oxygenase-2 expression and tumor proliferation, apoptosis and angiogenesis in patients with advanced stage high-grade ovarian carcinoma.


METHODS
Specimens from 118 patients with high-grade and advanced stage (III, IV) serous ovarian carcinoma were evaluated by immunohistochemistry for cyclo-oxygenase-2, Ki-67, vascular endothelial growth factor, and bcl-2 expression. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between cyclo-oxygenase-2 expression and clinicopathologic characteristics, tumor angiogenesis (tumor microvessel density and vascular endothelial growth factor expression), and tumor proliferation and apoptosis. The effect of cyclooxygenase-2 expression on patient survival was determined.


RESULTS
There was a significant positive correlation between cyclo-oxygenase-2 expression in tumor cells and markers of tumor proliferation and angiogenesis. In univariate survival analysis, high cyclo-oxygenase-2 and high Ki-67 expression showed a significant impact of on patient survival (P < .001). In multivariate regression analysis, only Ki-67 expression retained its significance as an independent poor prognostic factor (death hazard ratio, 2.0; 95% CI, 1.2-3.3; P < .001).


CONCLUSIONS
Expression of cyclo-oxygenase-2 correlates with tumor proliferation and tumor angiogenesis but not with apoptotic markers (bcl-2 expression) in high-grade, advanced-stage serous ovarian carcinoma.
Ali-Fehmi
Rouba
R
Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Morris
Robert T
RT
Bandyopadhyay
Sudeshna
S
Che
Mingxin
M
Schimp
Veronica
V
Malone
John M
JM
Munkarah
Adnan R
AR
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation; D051546:Cyclooxygenase 2; D018284:Cystadenocarcinoma, Serous / Q000401:mortality* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000401:mortality* / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases