The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, inasmuch as it may allow tumors to escape immune surveillance. We have observed reduced expression of HLA antigens in sporadic colon cancer and adenomas from familial adenomatous polyposis patients. We now studied the expression of HLA class I antigens in patients with sporadic adenomas, which are precursors of colorectal cancer. Expression of HLA class I antigens was studied by immunohistochemistry in (a) sporadic colon adenomas, (b) histologically normal mucosa distant from the adenomas, (c) histologically normal colonic mucosa from patients with history of sporadic colon adenomas, and (d) colonic mucosa from normal subjects. HLA class I antigen expression was moderately reduced in 56% and severely reduced in 44% of the adenomas; this reduction was significant when compared to controls (P < 0.0001). The reduction of HLA class I expression in adenomas was related to the grade of dysplasia of the adenomas. HLA class I expression of normal appearing mucosa was decreased in 76% of patients with adenoma (P < 0.0001) and in 54% of patients with history of adenoma (P < 0.005) compared to normal controls. These changes were antigen specific, inasmuch as the expression of carcinoembryonic antigen, a surface antigen, was not affected. Our findings suggest that reduced HLA class I expression is an early event in the cell transformation process from normal to neoplastic state, preceding in many cases the onset of histological changes. HLA class I could be potentially used as a premalignant marker in the colon.
Supported by a grant from the American Cancer Society (IM-594) and a gift from Biosys, SA (Ideal Group, Athens, Greece) to B. R.