Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac

Background-Sulindac regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP), although the mechanism of polyp regression is unclear. Aims-To determine whether differences occur in alteration of rectal epithel ial apoptotic index and expression of apoptosis related proteins in FAP pat ients treated with sulindac compared with placebo. Patients-Twenty one FAP patients; 12 had not undergone colectomy. Methods-Patients with FAP were treated with sulindac 150 mg orally twice a day for three months (n=10) or placebo (n=11). Colorectal polyp number was determined and biopsies of the normal rectal mucosa were performed before a nd after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface ep ithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were asse ssed semiquantitatively by immunohistochemistry. Results-Significant decreases in polyp number and in the apoptotic ratio we re seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was -46% in the sulindac gr oup and +13% in the placebo group (p=0.005). Mean percentage change in the apoptotic ratio was -8% and +25% in the sulindac and placebo treated patien ts, respectively (p=0.004). No differences in expression or compartmentalis ation of apoptosis related proteins were noted between treatment groups. Conclusions-Sulindac regression of colorectal adenomas is accompanied by al teration of the rectal epithelial apoptotic ratio with relative increase in apoptosis in surface cells compared with the deeper crypt. The utility of the apoptotic ratio as an intermediate biomarker for colorectal tumorigenes is deserves further study.