A germline hMSH2 alteration is unrelated to colonic microsatellite instability in patients with ulcerative colitis

Recently, a polymorphism in the hMSH2 DNA mismatch repair gene has been ass ociated with the development of dysplasia in ulcerative colitis (UC) patien ts. This polymorphism is of interest because DNA mismatch repair defects re sult in alterations in microsatellite stability. The current study was desi gned to determine whether this hMSH2 polymorphism associates with the devel opment of microsatellite instability and dysplasia in UC patients. The hMSH 2 genotype of 96 UC patients was determined by direct DNA sequencing. In ad dition, we examined 363 samples of colonic mucosa from 93 of these UC patie nts for microsatellite mutation by polymerase chain reaction (PCR) at eight loci, Three cases had insufficient DNA for microsatellite instability stud ies. The hMSH2 polymorphism was identified in 13 of the 96 patients examine d (13.5%). The polymorphism was observed in 7 of 46 patients with dysplasia (15.2%), and in 6 of 50 patients without dysplasia (12.0%). Microsatellite instability was identified in 35 tissue samples (25 regenerative, one inde finite for dysplasia, eight dysplasias, and one invasive carcinoma) from 26 patients. Two patients with microsatellite instability had the hMSH2 alter ation. The 11 remaining patients had the hMSH2 polymorphism, but no evidenc e of microsatellite mutations with any of the markers tested. We were unabl e to confirm the previously reported findings that the specific germline hM SH2 alteration represents a marker for increased risk of dysplasia in patie nts with UC, nor is it responsible for the development of microsatellite in stability in these patients. HUM PATHOL 30:8-12. Copyright (C) 1999 by W.B. Saunders Company.