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COX-2 Expression and Survival in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiotherapy and Celecoxib: A Quantitative Immunohistochemical Analysis of RTOG C0128
  1. Corinne M. Doll, MD*,
  2. Kathryn Winter, MSc,
  3. David K. Gaffney, MD, PhD,
  4. Janice K. Ryu, MD§,
  5. Anuja Jhingran, MD,
  6. Adam P. Dicker, MD, PhD,
  7. Joanne B. Weidhaas, MD, PhD#,
  8. Brigitte E. Miller, MD** and
  9. Anthony M. Magliocco, MD,
  1. *Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada;
  2. Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA;
  3. Department of Radiation Oncology, Huntsman Cancer Hospital, Salt Lake City, UT;
  4. §Radiological Associates of Sacramento, Sacramento, CA;
  5. Department ofRadiation Oncology, MD Anderson Cancer Center, Houston, TX;
  6. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA;
  7. #Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT;
  8. **Department of Gynecologic Oncology, Wake Forest University,Winston Salem, NC; and
  9. ††Department of Anatomical Pathology, Lee Moffitt Cancer Center, Tampa, FL.
  1. Address correspondence and reprint requests to Corinne M. Doll, MD, Department of Oncology, Tom Baker Cancer Centre, University of Calgary, 1331 29th St NW, Calgary, AB, Canada T2N 4N2. E-mail: Corinne.Doll{at}albertahealthservices.ca.

Abstract

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 II 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®). 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.

  • Cervical cancer
  • RTOG C0128
  • COX-2
  • CD34
  • Predictive markers

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Footnotes

  • Supported by RTOG U10 CA21661 and CCOP U10 CA37422 grants from the NCI and the Pennsylvania Department of Health 2004 Formula Grant 4100026182.

  • The authors declare no conflicts of interest.

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