Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma

Abstract

Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme in prostanoid biosynthesis and is involved in tumor progression. We investigated expression of COX-1 and COX-2 in cell lines and tumors from ovarian carcinomas. Expression of COX-2 mRNA and protein was detectable in three of five ovarian carcinoma cell lines and was inducible by interleukin-1␤ or phorbolester in a subset of cell lines. Prostaglandin E 2 (PGE 2 ) production could be inhibited by the selective COX-2 inhibitor NS-398. In malignant ascites of ovarian carcinomas significantly increased levels of PGE 2 were found compared to other carcinomas or nonmalignant ascites (P ‫؍‬ 0.03). We investigated expression of COX-2 by immunohistochemistry in 117 ovarian surface epithelial tumors. Expression of COX-2 was detected in 42% of 86 ovarian carcinomas and in 37% of 19 low malignant potential tumors, but not in 12 cystadenomas or 2 normal ovaries. Expression of COX-1 was detected by immunohistochemistry in 75% of 75 invasive ovarian carcinomas and in 75% of 16 low malignant potential tumors, whereas 2 samples from normal ovaries and 8 cystadenomas were positive for COX-1. In univariate survival analysis of invasive carcinomas, expression of COX-2 was associated with a significantly reduced median survival time (log rank test, P ‫؍‬ 0.04). For patients younger than 60 years of age, this association was even more significant (P < 0.004). In contrast, expression of COX-1 was no prognostic parameter (P ‫؍‬ 0.89). There was no significant correlation between COX-2 or COX-1 expression and other clinicopathological markers. In multivariate analysis expression of COX-2 was an independent prognostic factor for poor survival (relative risk, 2.74; 95% CI, 1.38 to 5.47). Our data indicate that COX-2 expression is an independent prognostic factor in ovarian carcinoma. Based on the results of this study, it would be interesting to

NSAIDs induce apoptosis in nonproliferating ovarian cancer cells and inhibit tumor growth in vivo

“…Decreased sensitivity to chemotherapy and poor prognostic outcome has been associated with ovarian carcinomas expressing COX-2 (24). However, it has been shown that COX-2 is only expressed in a subset of ovarian carcinomas (25).…”

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

“…15 Immunohistochemical staining of COX-2 was performed according to standard procedures as previously described. 16 To evaluate the specificity of the COX-2 antibody (Cayman Chemical, Ann Arbor, MI, USA) we and others have already performed blocking experiments with the COX-2 blocking peptide (Cayman Chemicals) according to the manufacturer's instructions. 15 In addition, we used control tissue and cell lines for control of immunohistochemical staining procedures.…”

La prostaglandine D2

“…Par ailleurs, un rôle important des prostaglandines endoperoxydases COX1 et COX2, de la prostaglandine E2 (PGE2) et de son enzyme de synthèse la prostaglandine E synthase (PGES), a été démontré dans la tumorigenèse ovarienne [42][43][44]. Nos études récentes ont montré une forte expression des partenaires de la voie de signalisation embryonnaire mâle L-PGDS/SOX9 dans des biopsies de tumeurs ovariennes humaines de différents types histologiques [45] ( Figure 3A).…”