Lewis Y antigen expression in hepatocellular carcinoma. An immunohistochemical study.

Abstract

The altered expression of the Lewis blood group-related antigens during malignant transformation can be used clinically as a tumor marker or as a prognostic indicator. The Lewis Y (LeY) antigen, which is one of the Type 2 human blood group-related antigens, also is thought to behave as an oncodevelopmental cancer-associated antigen. In this study, the authors examined the association between human LeY antigen expression and the clinicopathologic features of HCC, including its proliferative activity. Forty-six histologically confirmed cases of HCC were studied retrospectively. Liver biopsy specimens from the main tumor of each case were obtained under ultrasonic guidance before treatment was initiated. The formalin fixed, paraffin embedded serial sections were immunostained using a modification of the avidin-biotin-peroxidase complex method, with a primary monoclonal antibody (MoAb) directed against the LeY antigen (BM-1/JIMRO). The relationship between LeY antigen expression and the HCC's proliferative activity was analyzed similarly by immunohistochemical methods using a primary MoAb directed against the Ki-67 antigen (MIB 1). In addition, to clarify the relationship between LeY antigen expression and the histologic heterogeneity within HCC, seven cases of surgically resected HCC also were immunostained. The LeY antigen was detected on the membrane and in the cytoplasm of the cancer cells. Of the 46 HCC cases, 20 (43.5%) expressed the LeY antigen in the tumor cells. There was no correlation between LeY antigen expression and the maximum tumor dimension or the Stage. However, the incidence of LeY antigen-positive cases in poorly differentiated HCCs was found to be significantly higher than that in well or moderately differentiated HCCs (P < 0.01). In resected HCC cases, LeY antigen expression within HCC nodules was frequently greater in the less differentiated tumor than in adjacent differentiated tumor. Moreover, the incidence of LeY antigen expression in alpha-fetoprotein (AFP)-positive (AFP > or = 200 ng/ml) HCC cases was significantly higher than that in AFP-negative (AFP < 200 ng/ml) HCC cases (P < 0.05). Furthermore, the mean value of the Ki-67 labeling index in LeY antigen-positive HCC cases (25.2 +/- 11.3%) was significantly higher than that in LeY antigen-negative HCC cases (9.4 +/- 4.1%) (P < 0.001). These results suggest that LeY antigen expression correlated closely to the dedifferentiation and proliferative activity of HCC.