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Gut. 2010 May;59(5):622-9. doi: 10.1136/gut.2008.175406.

Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention.

Collaborators (151)

Benamouzig R, Uzzan B, Martin A, Deyra J, Little J, Girard B, Chaussade S, Barakrok N, Beujard E, Benamouzig R, Benazzouz AP, Benoit R, Berthelemy B, Blondon H, Bordet E, Boulant J, Bour B, Cassan P, Chaussade S, Ciribilli JM, Coudert P, Courillon-Mallet A, Danielou JY, Degoy J, Delasalle P, Delchier JC, Dieumegard B, Dreyfus G, Dupas JL, Durney D, Dusoleil A, Flamenbaum M, Flaubert, Fontanges T, Fourgeaud JL, Gatineau-Saillan G, Godeberge P, Goldfain D, Gouffier E, Grobost O, Heyman B, Heyries L, Humeau B, Kalinsky E, Kerneis J, Klewansky M, Kusielewicz D, Lagneau M, Lamarque D, Lepage M, Loiseau D, Macaigne O, Malka D, Marill JL, Marti R, Mitry E, Nalet B, Nizou C, Pariente EA, Paupard T, Perrot S, Pigot, Pouderoux P, Rampal P, Rautureau J, Renou C, Ribiere, Roche H, Rotenberg A, Rougier P, Rusniewski P, Schneider S, Souillac P, Stremsdoerfer N, Tainturier MH, Travers B, Vergeau B, Zamora C, Zummer R, Abarah B, Aillet G, Anger E, Balaton A, Barhoum K, Baron V, Benderitter-Giovo E, Bertrand G, Besnard-Bernadac MC, Bonnafous F, Bouc M, Bougaran J, Bringeon B, Cales V, Calvet E, Carayon MJ, Carnot F, Chamlian A, Chassaigne C, Chatelain D, Chomarat C, Cloup N, Coppe P, Costes-Chalret N, Cousin-Maignan C, Degott C, Dubois-Gordeff A, Durand L, Fabiani-Caetz B, Forest E, Giglio L, de Pinieux G, Gros P, Hofman-Guilaine C, Homsi T, Jeandel R, Journel B, Kalifat R, Karkouche B, Kerlo P, Lab P, Languille-Mimoune O, Lesec G, Longchampt E, Louis B, Marquet M, Martin A, Marty-Double C, Medioni LD, Molas G, Monnier P, Mosnier-Damet M, Nenert N, Petit J, Rey C, Richard-Coulet E, Rolachon J, Romeo JM, Roucayrol AM, Roux F, Saint-Paul MC, Schill H, Schlund-Schoettel E, Staroz S, Trincard MD, Tulliez M, Valade S, Verdier V, Verriele V, Zafrani E, Munoz N, Esteve J.

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 with 16/64 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.

PMID:
20427397
DOI:
10.1136/gut.2008.175406
[PubMed - indexed for MEDLINE]
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