CLINICAL TRIAL REPORT Cyclooxygenase-2 Expression and Recurrence of Colorectal Adenomas: Effect of Aspirin Chemoprevention Sarah Kraus & Nadir Arber Published online: 31 December 2010 # Springer Science+Business Media, LLC 2010 Benamouzig R, Uzzan B, Martin A, et al.; APACC Study Group: Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention. Gut 2010, 59:622–629. Rating: •Of importance. Introduction: Inducible cyclooxygenase-2 (COX-2) is a central mediator in inflammation and a key enzyme involved in several cellular processes that has been shown to be overexpressed in many premalignant, malignant, and metastatic cancers, including colorectal cancer (CRC). COX-2 is expressed at high levels in a large percentage of CRCs and in more than 80% of CRC metastases. Its overexpression correlates with tumor recurrence [1], ad- vanced stages of CRC [2], and serves as an independent prognostic factor in CRC patients [3]. COX-2 is a well known target of nonsteroidal anti- inflammatory drugs (NSAIDs), which appear to reduce the risk of developing cancer. Moreover, COX-2 inhibition is the main mechanism through which NSAIDs act to reduce tumor growth and carcinogenesis [4]. Previous investigations have shown that COX-2 is upregu- lated in colorectal adenomas. However, the percentage of adenomas expressing COX-2 varied among studies and its expression was partly associated with their size and degree of dysplasia [5], thereby suggesting that the role of COX-2 in CRC may be at an early stage in the adenoma-to-carcinoma sequence and supporting the idea that inhibition of COX-2 may be useful in the chemoprevention of the disease. The role of COX-2 expression in adenoma recurrence has not been thoroughly investigated. Moreover, the mechanisms by which NSAIDs and aspirin reduce the risk of CRC and adenoma recurrence are not fully elucidated. Prospective randomized studies in patients with familial adenomatous polyposis (FAP) have uniformly found that NSAIDs can produce regression of existing adenomas and prevent the formation of new polyps. NSAIDs have also been tested in large studies of patients at high risk of sporadic CRC, which showed that aspirin significantly reduces the risk of adenoma recurrence. The report by Benamouzig et al., discussed herein, presents the data obtained in a large series of colorectal adenomas, recruited from a double-blind randomized controlled trial (RCT) comparing recurrences after admin- istration of low-dose aspirin or placebo. It was shown that low-dose aspirin was associated with a lower incidence of adenoma recurrence after 1 and 3 years. Aims: The main objective of the study was to assess COX-2 expression, in relation to adenoma recurrence, independent- ly of aspirin use, and to examine the protective effect of aspirin in patients with adenomas expressing high levels of COX-2. Methods: Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. The samples were collected from patients who underwent colonoscopy and were recruited for a prospective RCT designed to determine the efficacy of regular aspirin intake (160 or 300 mg/day) in reducing colorectal adenoma recurrence [6]. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy. In addition, the architecture, grade of dysplasia, and the S. Kraus : N. Arber (*) Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel e-mail: nadir@tasmc.health.gov.il N. Arber e-mail: narber@post.tau.ac.il S. Kraus e-mail: sarahk@tasmc.health.gov.il Curr Colorectal Cancer Rep (2011) 7:5–7 DOI 10.1007/s11888-010-0081-y