Cyclooxygenase-2 (COX-2) levels before and after chemotherapy: a study in rectal cancer

Am J Clin Oncol. 2005 Dec;28(6):560-4. doi: 10.1097/01.coc.0000182476.34375.17.


Objectives: Induction of cyclooxygenase-2 (COX-2) by inflammatory mediators, oncogenes, and carcinogens has been demonstrated in preclinical models. However, there are limited clinical data regarding COX-2 induction by chemotherapy or radiation. Experimental data suggest cross-talk between the EGFR and COX-2 pathways. The aim of this study was to analyze the expression of COX-2 before and after chemoradiation (CRT) and correlate the same with tumor (T) down-staging and survival. Similar data were obtained for EGFR expression before and after chemoradiation.

Methods: Archival paraffin-embedded tumor specimens from patients undergoing CRT between 1995 and 2001 were analyzed. COX-2 expression was measured by immunohistochemistry (IHC), using the 160112 COX-2 mouse monoclonal antibody. For EGFR, we used mouse monoclonal Ab-10. Standard immunoperoxidase technique was used to detect the avidin- biotin peroxidase complex. Staining in tumor tissue was visually scored and confirmed by an image analyzer (ACIS; ChromaVision Medical Systems, Inc, San Juan Capistrano, CA).

Results: Twenty pretreatment biopsy samples from rectal cancer patients and their paired, post-CRT surgical specimens (n = 17) were analyzed. Three cases had no primary tumor after CRT. COX-2 expression was noted in 19 of 20 pretreatment samples and 17 of 17 surgical specimens. EGFR expression was noted in 10 cases pretreatment. Six patients with weakly positive COX-2 expression pretreatment had increased COX-2 expression after CRT, whereas in 1 patient the expression decreased after CRT. No EGFR induction was noted. There was no statistical association between EGFR and COX-2 expression in this data set. Median survival for the entire cohort was 38.9 months. There was no difference in survival between the COX-2 induced and noninduced groups.

Conclusions: COX-2 induction was seen with CRT in this population of rectal cancer patients. Prognostic significance of this induction remains to be defined in a larger cohort.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Biopsy
  • Cohort Studies
  • Combined Modality Therapy
  • Cyclooxygenase 2 / analysis*
  • Enzyme Induction
  • ErbB Receptors / analysis
  • Female
  • Fluorouracil / therapeutic use*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Life Tables
  • Male
  • Membrane Proteins / analysis*
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Prognosis
  • Proportional Hazards Models
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / enzymology*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Survival Analysis


  • Antimetabolites, Antineoplastic
  • Membrane Proteins
  • Neoplasm Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • ErbB Receptors
  • Fluorouracil