Microsatellite instability in inflamed and neoplastic epithelium in ulcerative colitis

Ishitsuka, T Kashiwagi, H Konishi, F

T. Ishitsuka et al., Microsatellite instability in inflamed and neoplastic epithelium in ulcerative colitis, J CLIN PATH, 54(7), 2001, pp. 526-532

25

INGLESE

Article

Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment

JOURNAL OF CLINICAL PATHOLOGY

0021-9746 → ACNP

54

7

2001

526 - 532

ISI

0021-9746(200107)54:7<526:MIIIAN>2.0.ZU;2-8

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 ions. 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.