大肠癌组织HLA-I类抗原及相关分子的表达意义

Expression of HLA molecule in colorectal cancer tissue

目的:探讨大肠癌组织HLA-Ⅰ类分子及相关分子表达及其意义. 方法:用免疫组化的方法,以切端黏膜作为正常对照,检测大肠癌组织、癌旁组织和正常黏膜组织中HLA-Ⅰ类分子及相关分子的表达,并结合肿瘤的临床病理资料综合分析. 结果:受检的大肠癌组织中重链HLA-A位点、B/C位点及轻链beta2微球蛋白(β2M)较其相应正常黏膜表达明显下调(P=0.0001);肠癌中低分子量多肽(LMP2)(P=0.0001),钙联蛋白(calnexin)(P=0.004)较正常黏膜表达明显下调;肠癌中HLA-Ⅰ类分子表达与肿瘤分化无关;随着肿瘤的Dukes 分期,癌组织中HLA-Ⅰ类分子表达渐次降低,但各位点表达情况并不相同,HLA-B/C表达水平与肿瘤分期相关,其在Dukes A期表达水平高于D期(P=0.0262). 结论:肠癌组织及癌旁黏膜中HLA-Ⅰ类分子、低分子量多肽及钙联蛋白较正常黏膜表达明显下调;肠癌组织中HLA- B/C位点随着肿瘤Dukes分期演进其表达下调.

AIM: To study the relationship between the expression of HLA class I and clinicopathological significance in colorectal cancers. METHODS: Expression of HLA class I and associated proteins was studied by immunohistochemistry in colorectal cancer, histologically normal mucosa adjacent to cancer (<3 cm), and histologically normal mucosa distant from cancer. Several monoclonal antibodies (mAbs) were used in this study: HC10 and HCA2 reacted with the nonmorphic determinant of heavy chain of HLA class I antigen; L368 reacted with β2 microglobulin; SY1 reacted with LMP2 antigen, and TO-5 reacted with calnexin. RESULTS: In colorectal cancer tissues, the expression of HLA -A,B/C, βM, LMP2 and calnexin were reduced compared to that of both in histologically normal mucosa adjacent to cancer and histologically normal mucosa distant from cancer (P =0.001).The expression of calnexin in cancer was also reduced compared to that of both in histologically normal mucosa adjacent to cancer and histologically normal mucosa distant from cancer (P =0.004). The expression of HLA-B/ C antigen in cancer was associated with diverse groups of pathological stage. With increase in Dukes staging of the cancer, the expression of HLA-B/C downregulated, in which that in Dukes A was higher than that in Dukes D (P=0.0262). CONCLUSION: The expression of HLA class I and associated protein is downregulated in the colorectal cancer tissue. It may be one important mechanism by which colorectal can- cer cell escapes immune surveillance.