Background-Several genetic alterations have been documented in dysplasia an
d cancer developing in ulcerative colitis (UC). However, the microsatellite
instability (MSI) status has rarely been described, especially in the infl
amed epithelium of UC.
Aims-To study MSI status during neoplastic and inflammatory changes in UC.
Methods-Seventy five surgically resected samples of colorectal mucosa, take
n from 16 colectomy specimens of patients with UC were examined: five patie
nts had a long duration with dysplasia or cancer (UC-LD with neoplasm), sev
en patients had a long duration without neoplastic changes (UC-LD without n
eoplasm), 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 mo
re loci (MSI greater than or equal to2) 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 gro
up (six of 14 v two of 23; p = 0.016). In the UC-LD without neoplasm group,
MSI greater than or equal to2 was detected significantly more frequently i
n patients with severe inflammation than in those with mild inflammation (s
ix 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 thr
ee of 17, and p53 overexpression was seen in 11 of 17 of the neoplastic les
Conclusions-A high incidence of MSI in long standing UC with severe inflamm
ation probably reflects genomic instability caused by repeated inflammatory
stress. Thus, the influence of inflammation should be considered when esti
mating MSI in UC. It is possible that changes in p53 expression are importa
nt in the development of cancer in UC.