Tsioulias G J, Triadafilopoulos G, Goldin E, Papavassiliou E D, Rizos S, Bassioukas P, Rigas B
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Cancer Res. 1993 May 15;53(10 Suppl):2374-8.
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.
肿瘤细胞HLA抗原的丢失被认为对肿瘤生长和转移很重要,因为它可能使肿瘤逃脱免疫监视。我们观察到散发性结肠癌以及家族性腺瘤性息肉病患者的腺瘤中HLA抗原表达降低。我们现在研究了散发性腺瘤患者(结直肠癌的前体)中HLA I类抗原的表达。通过免疫组织化学研究了HLA I类抗原在以下组织中的表达:(a)散发性结肠腺瘤,(b)距腺瘤较远的组织学正常黏膜,(c)有散发性结肠腺瘤病史患者的组织学正常结肠黏膜,以及(d)正常受试者的结肠黏膜。56%的腺瘤中HLA I类抗原表达中度降低,44%的腺瘤中严重降低;与对照组相比,这种降低具有显著性(P < 0.0001)。腺瘤中HLA I类表达的降低与腺瘤的发育异常程度有关。与正常对照组相比,76%的腺瘤患者(P < 0.0001)和54%的有腺瘤病史患者(P < 0.005)中外观正常黏膜的HLA I类表达降低。这些变化具有抗原特异性,因为癌胚抗原(一种表面抗原)的表达未受影响。我们的研究结果表明,HLA I类表达降低是细胞从正常状态向肿瘤状态转变过程中的早期事件,在许多情况下先于组织学变化的发生。HLA I类有可能用作结肠中的癌前标志物。