2336: Cyclooxygenase-2 Expression as a Predictor of Para-Aortic Lymph Node Recurrence in Uterine Cervix Cancer

Abstract

The overexpression of cyclooxygenase-2 (COX-2) is related to a worse prognosis and increased distant metastasis in cervix cancer. This case-control study examined whether COX-2 expression is a predictor of para-aortic lymph node (PAN) recurrence in uterine cervix cancer treated with radiation therapy. Between 1993 and 1999, 22 patients with PAN recurrence following curative (13 patients) or postoperative radiation therapy (9 patients) were enrolled as a study group. During the same period, another 22 patients who did not have PAN recurrence during a minimum 5-year follow-up were matched as a control group for FIGO stage. COX-2 expression in formalin-fixed paraffin-embedded tumor specimens taken before radiation therapy was assessed immunohistochemically using COX-2 mouse monoclonal antibody (Novocastra, UK). The staining threshold for a positive result was 1+ intensity in 10% of the tumor cells. The COX-2 immunostaining score was graded in four tiers according to the staining intensity in tumor tissues: 0, no staining; 1, weak staining; 2, moderate staining; 3, strong staining. A logistic regression model was used to predict PAN recurrence using the variables COX-2 expression, initial squamous cell carcinoma antigen (SCC) level, tumor size, and initial pelvic lymph node status. The staining scores were as follows: 0, 12 (27%); 1, 20 (46%); 2, 8 (18%); 3, 4 (9%). COX-2 was expressed in 32 (73%) of 44 patients. Patients with PAN recurrence had greater COX-2 expression in 19 (86%) compared with 13 (59%) in the control group (p=0.042). In the univariate analysis, predictive factors for PAN recurrence were COX-2 expression (p=0.027) and positive pelvic lymph nodes (p=0.008). In the multivariate analysis, significant predictive factors for PAN recurrence were positive pelvic lymph nodes (odds ratio 10.8, 95% confidence interval 2.0–58.1, p=0.006) and COX-2 expression (odds ratio 0.36, 95% confidence interval 0.14–0.9, p=0.03). This study suggests that COX-2 expression in the initial tumor tissues can be used as a predictive factor for para-aortic lymph node recurrence following radiation therapy in cervix cancer.