Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome

• Published in: Gynecologic oncology 2004-03, Vol.92 (3), p.806-812
• Main Authors: Raspollini, M.R, Amunni, G, Villanucci, A, Boddi, V, Baroni, G, Taddei, A, Taddei, G.L
• Format: Article
• Language: English
• Subjects: Adult; Aged; Chemotherapy response; Chemotherapy, Adjuvant; Cyclooxygenase 2; Disease-Free Survival; Female; Humans; Inducible nitric oxide synthase; Isoenzymes - biosynthesis; Membrane Proteins; Middle Aged; Neoplasm Staging; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Ovarian carcinoma; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Prognosis; Proportional Hazards Models; Prostaglandin-Endoperoxide Synthases - biosynthesis; Treatment Outcome
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2003.12.023

Objectives. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play a critical role in cancer development. We investigated iNOS and COX-2 expression in relation to clinical outcome in 78 International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian serous carcinoma with a low grade of differentiation (G3). Methods. Disease-free interval and cause-specific survival rates (Kaplan–Meier method) were compared using the log rank test. A multivariate analysis (Cox-proportional hazards models) was used to determine the independent effect of each variable on prognosis. Fisher's exact test was used to analyze the distribution of iNOS and COX-2 expression according to clinical complete response to chemotherapy and to the presence of a brief disease-free interval (≤12 months). Results. Overall 60 and 125 months cause-specific survival rates were 32% and 11%, respectively. In univariate analysis, iNOS ( P = 0.005 and P = 0.003, respectively), COX-2 ( P = 0.002 and P = 0.007, respectively), residual disease after surgery ( P = 0.017 and P = 0.032, respectively), and FIGO stage ( P = 0.008 and P = 0.025, respectively) were associated with survival and a disease-free interval. In multivariate analysis (Cox proportional hazards models), the factors that were found to be significantly independent predictors of disease relapse as well as survival were iNOS ( P = 0.014 and P = 0.001, respectively), COX-2 expression ( P = 0.007 and P = 0.029, respectively), and FIGO stage ( P = 0.026 and P = 0.05, respectively). iNOS and COX-2 expressions were correlated with a brief disease-free interval ( P = 0.001) and clinical complete response to first-line chemotherapy ( P = 0.038 and P = 0.033, respectively). Conclusions. The evaluation of iNOS and COX-2 expression may give additional prognostic information concerning the clinical outcome of patients with ovarian carcinoma and may encourage them to select more tailored therapies.