Increased Cyclooxygenase-2 Expression Is Associated With Chemotherapy Resistance and Poor Survival in Cervical Cancer Patients

Abstract

PURPOSE: To investigate the expression of cyclooxygenase (COX-2) and its association with clinicopathologic parameters and clinical outcome in patients with cervical cancer. PATIENTS AND METHODS: The study included 84 patients with stage IB to IVA cervical cancer. Patients with early-stage cases (n = 21) underwent radical surgery, whereas patients with locally advanced cervical cancer (LACC) (n = 63) were first administered neoadjuvant cisplatin-based treatment and subjected to surgery in case of response. Immunohistochemical analysis was performed on paraffin-embedded sections with rabbit antiserum against COX-2. RESULTS: COX-2–integrated density values in the overall population ranged from 1.2 to 82.3, with mean ± SE values of 27.4 ± 2.4. According to the chosen cutoff value, 36 (42.9%) of 84 patients were scored as COX-2 positive. COX-2 levels were shown to be highly associated with tumor susceptibility to neoadjuvant treatment. COX-2 showed a progressive increase from mean ± SE values of 19.9 ± 8.0 in complete responders through 31.5 ± 3.5 in partial responses to 44.8 ± 3.9 in patients who were not responsive (P = .0054). When logistic regression was applied, only advanced stage and COX-2 positivity retained independent roles in predicting a poor chance of response to treatment. COX-2–positive patients had a shorter overall survival (OS) rate than COX-2–negative patients. In patients with LACC, the 2-year OS rate was 38% in COX-2–positive versus 85% in COX-2–negative patients (P = .0001). In the multivariate analysis, only advanced stage and COX-2 positivity retained independent negative prognostic roles for OS. CONCLUSION: The assessment of COX-2 status could provide additional information to identify patients with cervical cancer with a poor chance of response to neoadjuvant treatment and unfavorable prognosis.