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COX‐2 expression is unexpectedly high in viable colorectal mucosal cells: is there life for chemoprophylaxis after VICTOR?
Author(s) -
McArthur D. R.,
Leung E.,
Morris A.,
Williams N.
Publication year - 2009
Publication title -
colorectal disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.029
H-Index - 89
eISSN - 1463-1318
pISSN - 1462-8910
DOI - 10.1111/j.1463-1318.2008.01662.x
Subject(s) - medicine , colorectal cancer , flow cytometry , proportional hazards model , chemoprophylaxis , adverse effect , cancer , cyclooxygenase , gastroenterology , immunology , enzyme , biochemistry , chemistry
Trials investigating colorectal cancer (CRC) chemoprophylaxis with cyclooxygenase‐2 (COX‐2) inhibitors have been discontinued because of adverse cardiovascular effects. Nevertheless, identification of patients where beneficial, chemo‐prophylactic effects of COX‐2 inhibitors outweigh side‐effects may be possible; this study aimed to investigate whether such patient groups might exist. Method The COX‐2 status of viable epithelial and inflammatory cells in freshly disaggregated CRC and paired normal colonic samples was assessed by three‐colour flow cytometry. Results 21/31 (67.7%) CRCs expressed COX‐2, with inflammatory cells positive in 19/31 (61.3%), epithelial cells in 12/31 (38.7%), and both positive in 10/31 (32.3%). 25/30 (83.33%) normal samples expressed COX‐2, with epithelial cells positive in 18/30 (60%), inflammatory cells in 15/30 (50%) and both positive in 10/30 (33.3%). Strength of expression by CRC and normal was similar. More advanced cancers had higher expression rates (COX‐2 in 12/13 (92.3%) with nodal disease vs 9/17 (52.9%) node‐negative; P = 0.04). Conclusion Investigation of ex‐vivo CRC cells by flow cytometry demonstrated COX‐2 expression rates comparable to that previously reported. However, expression by paired live normal colon was significantly greater, suggesting that COX‐2 may be expressed at higher rates in normal colonic cells in patients with CRC. Patients identified at resection as expressing COX‐2 in normal colon may benefit from Coxib chemo‐prophylaxis, thus potentially offering a refined approach to that adopted in the VICTOR trial.