Prognostic significance of proliferating cell nuclear antigen expression in hepatocellular carcinoma

Abstract

Background. Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in G 1/S-phase of the cell cycle and therefore is related to cell proliferative activity. In an attempt to evaluate its prognostic significance and clinicopathologic correlation in patients with hepatocellular carcinoma (HCC), the proliferative activity was studied using immunohistochemical staining with monoclonal antibody to PCNA. Methods. Seventy-two patients (64 men, 8 women; mean age, 52 years [range, 24-77 years]) having HCC surgically resected were studied. Tumor and nontumor tissues were selected from each case and stained with PCNA antibody. Tumor and nontumor PCNA (T-PCNA and NT- PCNA) scores were assessed by counting the positive staining nuclei per 1000 cells. Results. The T-PCNA score ranged from 10 to 894 per 1000 cells (mean ± standard deviation = 333 ± 263). It was found to be significantly and positively associated with positive margin (P = 0.003), direct liver invasion by tumor (P = 0.021), and venous permeation (P = 0.020), features directly or indirectly related to tumor invasiveness. However, it had no significant association with tumor size, cellular differentiation, or patients' hepatitis B surface antigen (HBsAg) status. When the tumors were stratified into two groups with a T-PCNA score less than or equal to 200 and a T-PCNA score greater than 200, those patients with a T-PCNA score less than or equal to 200 had significantly longer disease-free survival (DFS) and actual survival (AS) rates than those with scores greater than 200 (median DFS and AS, 34.6 and 49.3 months and 7.7 and 19.1 months, respectively; P = 0.019 and 0.035 for DFS and AS, respectively). T-PCNA and NT-PCNA scores had no significant correlation with the HBsAg status of the patients. Conclusions. Proliferative activity in HCC, as defined by PCNA immunohistochemical analysis, is significantly related to tumor invasiveness. It is also a potentially valuable prognostic factor in patients with this tumor.