Microsatellite instability in inflamed and neoplastic epithelium in ulcerative colitis

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Abstract
Background—Several genetic alterations have been documented in dysplasia and cancer developing in ulcerative colitis (UC). However, the microsatellite instability (MSI) status has rarely been described, especially in the inflamed epithelium of UC. Aims—To study MSI status during neoplastic and inflammatory changes in UC. Methods—Seventy five surgically resected samples of colorectal mucosa, taken from 16 colectomy specimens of patients with UC were examined: five patients had a long duration with dysplasia or cancer (UC-LD with neoplasm), seven patients had a long duration without neoplastic changes (UC-LD without neoplasm), and four patients had a short duration without neoplastic changes (UC-SD). In addition to MSI status examined by six microsatellite markers, p53 expression was compared among the three groups. Results—With regard to non-neoplastic inflamed epithelium, MSI in two or more loci (MSI≥2) was seen more frequently in the UC-LD without neoplasm group than in the UC-SD group (six of 14 v one of 12; p = 0.060), and significantly more often than in the UC-LD with neoplasm group (six of 14 v two of 23; p = 0.016). In the UC-LD without neoplasm group, MSI≥2 was detected significantly more frequently in patients with severe inflammation than in those with mild inflammation (six of nine v none of five; p = 0.028). With regard to neoplastic epithelium in the UC-LD with neoplasm group, MSI in two or more loci was found in three of 17, and p53 overexpression was seen in 11 of 17 of the neoplastic lesions. Conclusions—A high incidence of MSI in long standing UC with severe inflammation probably reflects genomic instability caused by repeated inflammatory stress. Thus, the influence of inflammation should be considered when estimating MSI in UC. It is possible that changes in p53 expression are important in the development of cancer in UC.