Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome.
OBJECTIVE
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 (< or =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.
Raspollini
M R
MR
Department of Human Pathology and Oncology, University of Florence, Florence, Italy.
Amunni
G
G
Villanucci
A
A
Boddi
V
V
Baroni
G
G
Taddei
A
A
Taddei
G L
GL
D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D051546:Cyclooxygenase 2; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D016016:Proportional Hazards Models; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D016896:Treatment Outcome
D007527:Isoenzymes; D008565:Membrane Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases