KI-67 ANTIGEN EXPRESSION IN HEPATOCELLULAR-CARCINOMA USING MONOCLONAL-ANTIBODY MIB1 - A COMPARISON WITH PROLIFERATING CELL NUCLEAR ANTIGEN

To evaluate the prognostic significance and clinicopathologic correlat ion of proliferative activity in patients with hepatocellular carcinom a, Ki-67 antigen expression was examined using immunohistochemical sta ining with monoclonal antibody MIB1. Seventy-two patients (65 men, 7 w omen; age range 24-77 years, mean, 52 years) having hepatocellular car cinoma surgically resected were studied. Tumor and nontumorous tissues were stained with monoclonal antibody MIB1 with microwave oven pretre atment. Tumor and nontumor MIB1 (T-MIB1 and NT-MIB1) scores were asses sed by counting the positive staining nuclei per 1,000 cells. The T-MI B1 score ranged from 5-630 per 1,000 cells (mean +/- standard deviatio n [SD] = 145 +/- 162). It was found to be significantly higher in less well-differentiated tumors (Edmondson's grades III and IV) than in we ll-differentiated ones (Edmondson's grades I and II) (P =.017). The T- MIB1 score was also higher in nonencapsulated tumors than in encapsula ted ones, although it did not reach statistical significance (P =.069) . It had no influence on tumor size, tumor invasiveness, the backgroun d disease in the nontumorous livers, patients' HBsAg status, or serum cu-fetoprotein levels. Diseases in the nontumorous livers or patients' HBsAg status had no influence on the NT-MIBI scores. When the tumors were stratified into two groups with T-MIBI score less than or equal t o 20 and T-MIB1 score > 20, those patients with score less than or equ al to 20 had significantly longer disease-free survival (DFS) than tho se with scores > 20 (median DFS: 34 months and 4.7 months, respectivel y; P =.011). In addition, MIB1 and PCNA were closely correlated (P <.0 1). The authors conclude that proliferative activity in hepatocellular carcinoma, as defined by MIB1 immunohistochemical analysis, is signif icantly related to tumor cellular differentiation, It is also a potent ially valuable prognostic factor in patients with this tumor.