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

Abstract

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 alpha-foetoprotein (alphaFP) (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 alphaFP(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.