The effect of cyclooxygenase‐2 expression on tumor vascularity in advanced stage ovarian serous carcinoma

Publisher Website
Google Scholar
Abstract
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. Cancer 2003;98:1423–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11650