title: COX-2 expression and survival in patients with locally advanced cervical cancer treated with chemoradiotherapy and celecoxib: a quantitative immunohistochemical analysis of RTOG C0128.
abstract: OBJECTIVE
  This study aimed to measure expression of cyclooxygenase-2 (COX-2) and CD34 in pretreatment tumor biopsies from patients on the RTOG C0128 phase II study, and to correlate expression of these biomarkers, using quantitative immunohistochemistry, with clinical outcome parameters.
  
  
  METHODS
  Pretreatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative immunohistochemistry (AQUA®). 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.
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Corinne.Doll@albertahealthservices.ca
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Doll
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
authors.forename: David K
authors.initials: DK
authors.lastname: Gaffney
authors.forename: Janice K
authors.initials: JK
authors.lastname: Ryu
authors.forename: Anuja
authors.initials: A
authors.lastname: Jhingran
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Weidhaas
authors.forename: Brigitte E
authors.initials: BE
authors.lastname: Miller
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality* / Q000628:therapy*; D000068579:Celecoxib; D059248:Chemoradiotherapy / Q000379:methods; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality* / Q000628:therapy*; D055815:Young Adult
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib