Defective hMSH2/hMLH1 protein expression is seen infrequently in ulcerative colitis associated colorectal cancers

Background-Ulcerative colitis is associated with an increased risk of color ectal cancer above that of the normal population. The relative risk correla tes with the extent and duration of the disease but the genetic basis of ul cerative colitis associated cancer risk is not known. Aims-To assess the prevalence of microsatellite instability and mismatch re pair gene abnormalities in ulcerative colitis associated colorectal cancer. Patients-Forty six patients with colorectal cancer, with a previous histolo gical diagnosis of ulcerative colitis. Methods-The frequency of microsatellite instability and/or immunohistochemi cal expression of hMSH2 and hMLH1 was assessed. Thirty three cases were inv estigated using both approaches. Results-Although 6/41 (14.6%) cases showed microsatellite instability at on e or more markers, only one case (2.4%) exhibited high level instability (a t least two markers affected). Of 38 cases which were assessed using antibo dies against hMSH2 and hMLH1, only one case (2.6%) showed loss of expressio n. This case, which showed loss of hMSH2 expression, was the same case whic h exhibited high level microsatellite instability. The 33 cases which were investigated using both approaches showed that loss of expression of either hMSH2 or hMLH1 was not seen in any case which exhibited microsatellite ins tability in no more than one marker. Conclusions-This study suggests that both high level microsatellite instabi lity and loss of expression of hMSH2/hMLH1 are infrequent events in ulcerat ive colitis associated colorectal cancers. Low level microsatellite instabi lity was not associated with loss of expression of either hMSH2 or hMLH1.