Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy.
OBJECTIVE
To investigate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cervical cancer and their association with clinical outcome in patients treated with radical radiotherapy.


METHODS
One hundred sixty-seven consecutive patients with FIGO Stages IB-IVA squamous cell cervical cancer underwent radical radiotherapy, including external-beam radiotherapy or high-dose-rate brachytherapy, or both, between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and evaluate the effects of the factors affecting patient survival.


RESULTS
Positive immunostainings of iNOS and COX-2 were observed in 58.7% and 64.1% of the participants, respectively. The expression of both iNOS and COX-2 was positively correlated (Spearman correlation coefficient = 0.49, p < 0.01), and their overexpression provided independent predictors of distant metastasis (odds ratio = 5.22 and 10.07, respectively; p < 0.01 for all). iNOS- and COX-2-expressing patients had significantly shorter disease-free survival (p < 0.01, both) and cause-specific overall survival (p = 0.01, p < 0.01, respectively). Patients with iNOS-positive/COX-2-positive tumors had the poorest survival rates. Coexpression of iNOS/COX-2, together with bulky tumor and advanced stage were independent prognostic factors for disease-free survival.


CONCLUSIONS
Overexpression of iNOS or COX-2 or both was associated with decreased survival and a greater propensity to metastasize in cervical cancer patients treated with radiotherapy. Coexpression of iNOS and COX-2 may represent a useful biologic marker in patients receiving radical radiotherapy for cervical cancer.
Chen
Helen H W
HH
Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Su
Wu-Chou
WC
Chou
Cheng-Yang
CY
Guo
How-Ran
HR
Ho
Sheng-Yow
SY
Que
Jenny
J
Lee
Wen-Ying
WY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality / Q000532:radiotherapy; D051546:Cyclooxygenase 2 / Q000097:blood*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000097:blood*; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000532:radiotherapy
D009363:Neoplasm Proteins; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2