Invariant chain expression in colon neoplasms

Invariant chain (Ii) is a chaperone molecule that inhibits binding of endog enous antigens to class II molecules. High levels of Ii in cancer cells may prevent tumour antigen expression with class II and render the tumour less immunogenic. To correlate the expression of Ii and class II molecules in c olon carcinomas with the density of tumour infiltrating lymphocytes (TILs), surgical specimens from a total of 48 patients with well-(WDAC), moderatel y (MDAC) and poorly differentiated adenocarcinomas (PDAC), adenoma with hig h-grade dysplasia (AdHGD) and adenomas were immunostained for Ii and class II antigen (HLA-DR). Aggregates of TILs were graded in H&E-stained sections . Normal colon epithelium was negative for Ii and HLA-DR. Invasive carcinom as showed a linear increase in the expression of Ii in the progression from low- to high-grade tumours, while there was no significant difference in H LA-DR expression across the groups. Invasive carcinomas showed a disproport ionate increase in Ii over HLA-DR. Frequency of TILs showed inverse correla tion with expression of Ii and tumour grade. This is the first demonstratio n that expression of Ii increases in the progression from low- to high-grad e colon neoplasms and is most marked in the poorly differentiated carcinoma s. Ii expression by carcinomas is inversely related to the frequency of TIL s. The findings suggest that increased Ii renders the tumour less immunogen ic and less likely to stimulate a host immune response.