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

From the Departments of Obstetrics and Gynecology, Pathology, and Histology, Catholic University of the Sacred Heart, Rome, Italy.

Address reprint requests to Franco O. Ranelletti, Department of Histology, Catholic University, L. go F. Vito, 1, 00168 Rome, Italy; email: ranelletti{at}rm.unicatt.it

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.

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