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Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention
  1. Robert Benamouzig1,
  2. Bernard Uzzan2,
  3. Antoine Martin3,
  4. Jacques Deyra4,
  5. Julian Little4,
  6. Bernard Girard4,
  7. Stanislas Chaussade5,
  8. for the APACC Study Group
  1. 1Department of Gastroenterology, AP-HP, Hôpital Avicenne, Bobigny, France
  2. 2Department of Pharmacology, AP-HP, Hôpital Avicenne, Bobigny, France
  3. 3Department of Pathology, AP-HP, Hôpital Avicenne, Bobigny, France
  4. 4APACC Study Group
  5. 5Department of Gastroenterology, AP-HP, Hôpital Cochin, Paris Cedex, France
  1. Correspondence to Professor Robert Benamouzig, Department of Gastroenterology, AP-HP, Hôpital Avicenne, 125 route de Stalingrad, 93009 – Bobigny, France; robert.benamouzig{at}avc.aphp.fr

Abstract

Background Low-dose aspirin reduces the incidence of colorectal cancer and recurrence of adenomas. Cyclooxygenase-2 (COX-2), one of its main target enzymes, is reportedly over-expressed in colorectal adenomas.

Aim To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo.

Methods Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy, separately for epithelium, deep stroma and overall. Architecture, grade of dysplasia, K-ras mutation, p53 and cyclin D1 expression were studied.

Results COX-2 expression could be assessed in 219 adenomas from 136 patients: 128 adenomas (58%) from 59 patients strongly expressed COX-2. Strong COX-2 expression predominated in adenomas larger than 10 mm (84/129 vs 44/90; p=0.02) and in adenomas showing high-grade dysplasia (22/29 vs 104/188; p=0.04). Deep stromal but not epithelial initial expression of COX-2 predicted adenoma recurrence in the whole population (30/72 patients or 42% strongly expressed deep stromal COX-2 compared with16/64 or 25% without recurrent adenoma; p=0.04). The protective effect of aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR for recurrence in patients taking aspirin with low COX-2 expression: 0.59; 95% CI 0.39 to 0.90; p=0.02). There was no significant effect of aspirin at the end of the trial.

Conclusion Over-expression of COX-2 was frequent and predominated in large and high-grade dysplasia adenomas. Deep stromal but not epithelial initial expression of COX-2 predicted recurrence of adenomas. Aspirin did not act preferentially on patients whose initial adenomas strongly expressed COX-2.

  • Aspirin
  • randomised controlled trial
  • colorectal adenoma
  • colorectal cancer
  • cancer prevention
  • COX-2 expression
  • carcinogenesis
  • chemoprevention
  • RCT
  • randomised controlled trial
  • CRC
  • colorectal cancer
  • COX-2
  • cyclooxygenase-2
  • NSAID
  • non-steroidal anti-inflammatory drug

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Footnotes

  • Funding The study was support by grants from the French Ministry of Health (PHRC), the Association pour la Recherche contre le Cancer (ARC), and the Société Nationale Française de Gastro-Entérologie (SNFGE).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Saint Germain en Laye Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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