The effect of cyclooxygenase-2 expression on tumor vascularity in advanced stage ovarian serous carcinoma.
BACKGROUND
Cyclooxygenase-2 (COX-2) seems to be involved at various steps in the processes of malignant transformation and tumor progression. Investigations have shown that COX-2 overexpression is associated with increased proliferation, reduced apoptosis, and angiogenesis.


METHODS
Specimens from 125 patients with high-grade, advanced-stage (Stage III-IV) serous ovarian carcinoma were evaluated by immunohistochemistry for COX-2, p53, bcl-2, epidermal growth factor receptor (EGFR), and Her-2/neu expression and for CD34-stained microvessel density (MVD). Statistical analysis was performed to investigate the correlations between COX-2 expression and 1) clinicopathologic characteristics, 2) tumor MVD, and 3) expression of other molecular markers. The effect of COX-2 expression on survival was determined using survival analysis.


RESULTS
Increased COX-2 expression was significantly correlated with tumor MVD (Spearman rank correlation test: r = 0.41; P < 0.001). There was no association observed between COX-2 expression and expression levels of EGFR, Her-2/neu, bcl-2, or p53. Patients who had tumors that showed high COX-2 expression had a worse prognosis compared with patients who had tumors with low expression (death hazard ratio, 2.0; 95% confidence interval, 1.2-3.5; P < 0.001). A multivariate analysis revealed that COX-2 expression was the strongest predictor of survival among the different prognostic factors analyzed.


CONCLUSIONS
The current study demonstrated that COX-2 expression was correlated significantly with survival in patients with high-grade, high-stage serous ovarian carcinoma. Expression of COX-2 also was correlated with tumor angiogenesis but not with EGFR, Her-2/neu, or p53 expression. In addition to their prognostic significance, a better understanding of the biology of these molecular changes may help identify new targets for therapy in patients with ovarian carcinoma.
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D015331:Cohort Studies; D018293:Cystadenoma, Serous / Q000401:mortality / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor; D011451:Prostaglandin-Endoperoxide Synthases