Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac

被引:59
作者
Keller, JJ
Offerhaus, GJA
Polak, M
Goodman, SN
Zahurak, ML
Hylind, LM
Hamilton, SR
Giardiello, FM
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[4] Acad Med Ctr, Dept Pathol, Amsterdam, Netherlands
关键词
apoptosis; familial adenomatous polyposis; sulindac; intermediate biomarker; tumorigenesis;
D O I
10.1136/gut.45.6.822
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 epithelial apoptotic index and expression of apoptosis related proteins in FAP patients 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 and after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface epithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were assessed semiquantitatively by immunohistochemistry. Results-Significant decreases in polyp number and in the apoptotic ratio were seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was -46% in the sulindac group 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 patients, respectively (p=0.004). No differences in expression or compartmentalisation of apoptosis related proteins were noted between treatment groups. Conclusions-Sulindac regression of colorectal adenomas is accompanied by alteration 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 tumorigenesis deserves further study.
引用
收藏
页码:822 / 828
页数:7
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