COX-2 Expression and Survival in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiotherapy and Celecoxib A Quantitative Immunohistochemical Analysis of RTOG C0728

Purpose: This study aimed to measure expression of cyclooxygenase-2 (COX-2) and CD34 in pretreatment tumor biopsies from patients on the RTOG C0128 phase H study, and to correlate expression of these biomarkers, using quantitative immunohistochemistry, with clinical outcome parameters. Methods and Materials: Pretreatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative immunohistochemistry (AQUA (R)). Cox regression models and Fisher's exact test were used to explore associations between expression of the biomarkers and clinical end points. Results: Eighty-four patients were accrued between 2001 and 2004; 78 were eligible and analyzable. Pathology specimen submission was optional; COX-2 expression was determined for 37 (47%) of patients, and CD34 scoring was determined for 34 (44%) of patients. Median follow-up was 44.5 months. In tumors where COX-2 data were available, 6 (16%) of 37 patients had local-regional failure; 4 of these patients had tumors with COX-2 scores below the AQUA score median (hazard ratio, 0.39; 95% confidence interval, 0.07-2.16; P = 0.28). Of the 8 patients with disease-free survival failures, 5 had tumors with COX-2 levels below the median (hazard ratio, 0.49; 95% confidence interval, 0.12-2.04; P = 0.32). The 4 patients who died all had COX-2 levels below the median value. COX-2 levels below the median were associated with worse 2-year survival (Fisher's P = 0.046). There was no statistically significant association between CD34 status and clinical outcome. Conclusions: Low COX-2 expression measured by AQUA was associated with worse overall survival in this subset of patients available for analysis from RTOG C0128. Application of AQUA technology, in a larger study, will be required to definitively evaluate the association COX-2 with clinical outcome in cervical cancer.