P21/WAF1 is an independent survival prognostic factor for patients with hepatocellular carcinoma after resection.

Background/Aims: The cyclin kinase inhibitor p21/WAF1 is regulated by p53-dependent or independent pathways and inhibits the action of proliferating cell nuclear antigen (PCNA). The prognostic role of p21/WAF1 in hepatocellular carcinoma (HCC) is ambiguous. To further clarify this, we examined the expression of three genes in HCC. Methods: A total of 122 resected HCC specimens were collected from 1987 to 1998. Expression of p21/WAF1, p53, and PCNA in HCC was analysed by immunohistochemistry. Results: Immunoreactivity was detectable for p21/WAF1 in 37%, and for p53 in 41.8% of HCCs. Positive expression of both genes does not relate to each other, but both are associated with a high PCNA labelling index (LI) ( P<0.05) in tumour. p53 (+) is also associated with high serum α-foetoprotein (αFP) ( P<0.001), tumour dedifferentiation ( P=0.001) and advanced pathologic stages ( P=0.017). However, p21/WAF1 (+) did not show clinicopathologic significance. Survival analysis indicated that poor prognostic factors were p21/WAF1 (−) ( P=0.024), p53 (+) ( P=0.008), high PCNA ( P<0.001), tumour without capsule ( P=0.001), poor tumour differentiation ( P=0.004), advanced pathologic stage ( P<0.001), and high serum αFP( P<0.001). Independent factors were p21/WAF1 expression, pathologic stage, and PCNA. Conclusion: In HCC, increased proliferation index PCNA is significantly associated with positive p53 and p21/WAF1. But p21/WAF1 expression did not relate to p53 expression. P21/WAF1 (+) is a good event and serves as an independent survival prognostic factor for HCC, which is a novel finding apart from previous reports. [ABSTRACT FROM AUTHOR]