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 correlation of proliferative activity in patients with hepatocellular carcinoma, Ki-67 antigen expression was examined using immunohistochemical staining with monoclonal antibody MIB1. Seventy-two patients (65 men, 7 women; age range 24-77 years, mean, 52 years) having hepatocellular carcinoma surgically resected were studied. Tumor and nontumorous tissues were stained with monoclonal antibody MIB1 with microwave oven pretreatment. Tumor and nontumor MIB1 (T-MIB1 and NT-MIB1) scores were assessed by counting the positive staining nuclei per 1,000 cells. The T-MIB1 score ranged from 5-630 per 1,000 cells (mean +/- standard deviation [SD] = 145 +/- 162). It was found to be significantly higher in less well-differentiated tumors (Edmondson's grades III and IV) than in well-differentiated ones (Edmondson's grades I and II) (P = .017). The T-MIB1 score was also higher in nonencapsulated tumors than in encapsulated ones, although it did not reach statistical significance (P = .069). It had no influence on tumor size, tumor invasiveness, the background disease in the nontumorous livers, patients' HBsAg status, or serum alpha-fetoprotein levels. Diseases in the nontumorous livers or patients' HBsAg status had no influence on the NT-MIB1 scores. When the tumors were stratified into two groups with T-MIB1 score < or = 20 and T-MIB1 score > 20, those patients with score < or = 20 had significantly longer disease-free survival (DFS) than those with scores > 20 (median DFS: 34 months and 4.7 months, respectively; P = .011). In addition, MIB1 and PCNA were closely correlated (P < .01). The authors conclude that proliferative activity in hepatocellular carcinoma, as defined by MIB1 immunohistochemical analysis, is significantly related to tumor cellular differentiation. It is also a potentially valuable prognostic factor in patients with this tumor.