Gene analysis of aberrant crypt foci in patients with ulcerative colitis

目的：目的探讨结肠镜下异常隐窝病灶（ACF）作为结肠癌生物标志物的意义，并分析其基因改变，以证实其是溃疡性结肠炎（UC）患者结肠癌发生的先兆病变。UC患者的ACF平均数为8.7±3.7，明显高于正常人。特别是在UC患者中，异型增生明显高于无异型增生。ACF的数目与异型增生的阳性率有显著相关性（p<0.01）。ACF和UC患者异型增生中K-ras基因突变较少。在ACF和异型增生中未检测到APC和β-catenin异常。p53蛋白在ACF中未见异常表达，而在异型增生中有异常表达。p16基因启动子甲基化在UC患者ACF和异型增生中较常见。结论：ACF可作为UC患者结直肠癌监测的一个有用的生物标志物，ACF可能是结肠癌发生过程中异型增生的一个先兆病变。

Aim : To investigate the significance of aberrant crypt foci (ACF), which could be identified by magnifying endoscopy, as a biomarker in colitic cancer, and to analyze gene alterations in order to demonstrate it is a precursor lesion in colorectal carcinogenesis of the patients with ulcerative colitis (UC).Methods and Results : ACF was identified using magnifying endoscope (Fujinon 485, ZW) with the aid of methylene blue. The mean number of ACF in patients with UC was 8.7±3.7, being significantly higher than that of normal subjects. In particular, it was significantly higher in UC patients with dysplasia than that without dysplasia. The number of ACF was significantly correlated with the positivity of dysplasia (p<0.01). There were few mutations of K-ras in ACF and dysplasia of UC patients. No APC and beta-catenin abnormality was detected in ACF or dysplasia. No p53 abnormality was detected in ACF, but was in dysplasia. Hypermethylation of p16 gene promoter was frequently detected in ACF and dysplasia in UC patients. Now gene analysis with microarray in ACF and dysplasia are underway.Conclusion : It was demonstrated that ACF could serve as a useful biomarker for surveillance of colorectal cancer in UC patients, and that ACF might be a precursor lesion of dysplasia in colitc carcinogensis.