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

Abstract

Microsatellite-instability-positive (MSI+) colorectal cancers are characterised by an accumulation of deletion and insertion mutations at simple repeated sequences caused by inactivation of mismatch repair proteins. They share several clinicopathological features, including a better prognosis and a pronounced stromal inflammatory reaction. We have used suppression subtraction hybridisation between normal colonic epithelium and paired carcinomas to 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. This was in contrast to the MSI(-) tumour screen, where none of the clones analysed expressed this class of gene. Our results confirm that MSI(+) tumours may have a greater potential for the efficient presentation of antigens to the helper arm of the immune system and lend further support to the theory that the better prognosis of patients with MSI+ tumours may be linked to an enhanced immunogenicity of these tumours.