Microsatellite instability and loss of heterozygosity in the nondysplastic colonic epithelium of ulcerative colitis

Abstract

Background. A major longterm risk for patients with ulcerative colitis (UC) is the development of colorectal dysplasia and cancer. Microsatellite instability (MI) has now been reported not only in colitic cancers but also in dysplasias, and even in nondysplastic inflamed mucosa. With the conventional microdissection technique, however, contamination by nonepithelial cells cannot be prevented and this could produce less reliable results than other methods. Therefore, we examined the condition of MI and loss of heterozygosity (LOH) of UC epithelium using a crypt isolation technique. Methods. One hundred and twenty-nine biopsy samples from 21 patients with UC were investigated for histology and microsatellite status, using nine microsatellite markers. A total of 1031 polymenase chain reaction (PCR) products were evaluated. Results. We found that no microsatellite markers displayed instability, but LOH at the 3p locus was detected in the nondysplastic epithelium of one patient with longstanding UC. Conclusions. Our study strongly suggests that MI does not contribute to the progression of the colitis-dysplasia sequence.

Microsatellite instability in long-standing ulcerative colitis

“…This is in agreement with other studies that did not find MSI in non-neoplastic lesions [11,16,19]. However, Brentnall et al [15] and Noffsinger et al [31] detected MSI in 50% and 9% of non-dysplastic mucosa, respectively.…”

Hypermethylation of p14 ARF May Be Predictive of Colitic Cancer in Patients with Ulcerative Colitis

“…14,18,19 Takahashi et al 19 suggested that such discrepancies may be partially attributed to the degeneration of DNA obtained from formalin-fixed tissues. In the present investigation, using DNA obtained from frozen tissue specimens, we identified MSI in one of five dysplasias and in none of the nonneoplastic mucosa.…”

“…Although our sample size was small, the incidence of MSI in the colonic neoplasia was not obviously different from that in patients without UC. 19 It seems possible that MSI does not have an important role in the development of dysplasia in UC. It has been recently confirmed that flat dysplasia in UC can be detected by chromoendoscopy and fluorescence endoscopy.…”

“…[12][13][14][15] In addition, some investigators have reported MSI to be found even in nonneoplastic mucosa of UC, [15][16][17] although controversial results have been shown by other investigators. 14,18,19 Little data has yet been published on the hypermethylation of INK4a/ARF and MSI in the nonneoplastic mucosa of UC. Furthermore, possible correlations between such genetic or epigenetic abnormalities and the clinical features of UC have not yet been examined precisely.…”