Significance Of Abnormal HLA Molecules Expression In Colorectal Carcinoma

OBJECTIVE: To study the relationship between the expression of HLA molecules and clinicopathological significance in colorectal cancinoma.METHODS: Expressions of HLA class I and associated antigens were studied by immunohistochemistry in colorectal cancinoma, histologically normal mucosa adjacent to cancinima(<3cm),and histologically normal mucosa distant from cancinoma. The density of variety leukocytes in the tissue of cancinoma was studied also. 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 ?2 microglobulin; SY1 reacted with LMP2 antigen;TO-5 reacted with calnexin;CD8 and S-100 reacted with T cells and DC.RESULTS: In colorectal cancinoma tissues, the expression of HLA –A, B/C, ?2M, LMP2 and calnexin were reduced compared to that of both in histologically normal mucosa adjacent to cancinoma and histologically normal mucosa distant from cancinoma(P=0.001).The expression of calnexin in cancinoma were reduced compared to that of both in histologically normal mucosa adjacent to cancinoma and histologically normal mucosa distant from cancinoma also(P=0.004). With the cancinoma Dukes phaging, the expression of HLA-B/C downregulated, which in Dukes A is higher than that in Dukes D(P=0.0262). 16.9% colorectal cancinoma expressed the HLA-II antigen, and the expression of the HLA class II molecules in the colorectal cancinoma was reduced compared to the normal tissue (P=0.001). With the Dukes staging of the colorectal cancinoma, the HLA-I antigen and the density of leukocytes and CTL reduced. With degree of colorectal differentiation, the density of DC dereased.CONCLUSION: The expression of HLA class I and associated protein were downregulated in the colorectal cancinoma tissue. It may be one important mechanism by which colorectal cancinoma cell escape from immune recognition. The calnexin,a kind of the chaperone molecules,and the LMP2,one of the antigen process molecules, expression downregulated in colorectal cancer,these antigens may effect the HLA class I molecules expression in the colorectal cancinoma. The results of density of dendritic cells declined and HLA class II expression downregulation suggested that potential of antigen process and present in the cancinoma was reduced compared to the normal tissue. The abnormality may provide tumor cells with a mechanism to escape from immune surveillance; With the Dukes staging of the colorectal cancinoma, the potential of host immunity declined and the potential of the colorectal cancinoma escape from immunity surveillance inreased. we follow up these patients, and the results showed that these patients with HLA downregulation have bad prognosis.