Gene analysis of aberrant crypt foci in patients with ulcerative colitis

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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.