Expression of HLA class II in colorectal cancer: Evidence for enhanced immunogenicity of microsatellite-instability-positive tumours

Microsatellite-instability-positive (MSI+) colorectal cancers are character ised by an accumulation of deletion and insertion mutations at simple repea ted sequences caused by inactivation of mismatch repair proteins. They shar e several clinicopathological features, including a better prognosis and a pronounced stromal inflammatory reaction. We have used suppression subtract ion hybridisation between normal colonic epithelium and paired carcinomas t o generate differential gene expression profiles in MSI+ and MSI- tumours. Following reverse northern blotting analysis, 11 genes were found to be up- regulated in the MSI+ tumour, and one of these specified the HLA-DM gene. T his was in contrast to the MSI- tumour screen, where none of the clones ana lysed expressed this class of gene. Our results confirm that MSI+ tumours m ay have a greater potential for the efficient presentation of antigens to t he helper arm of the immune system and lend further support to the theory t hat the better prognosis of patients with MSI+ tumours may be linked to an enhanced immunogenicity of these tumours. Copyright (C) 2001 S. Karger AG, Basel.