Gene analysis of aberrant crypt foci in patients with ulcerative colitis

目的：探讨异常隐窝灶(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ACF是溃疡性结肠炎(UC)患者结直肠癌发生的前驱病变。UC患者平均ACF数为8.7±3.7，显著高于正常对照组。尤其是UC伴异型增生患者显著高于无异型增生患者。ACF的数量与异型增生的阳性率显著相关(p&lt；0.01)。UC患者ACF和异型增生组织中K-ras基因突变较少。ACF和异型增生均未检测到APC和β-连环素异常。ACF组织中未见P53异常表达，异型增生组织中P53蛋白表达异常。P16基因启动子高甲基化多见于ACF和UC异型增生。结论：ACF可作为监测UC患者结直肠癌的有用生物标志物，ACF可能是结肠癌发生过程中不典型增生的前驱病变。

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.