Background: The cyclin dependent kinase p21waf1 plays a crucial role in the regulation of cell cycle. The family of p53 proteins has the ability to induce p21waf1, whereas p16INK4a modulates post-transcriptionally the expression of p21waf1. Methods: Total 36 hepatocellular carcinomas (HCCs) and 24 paired adjacent liver tissues were evaluated for the following: (1) expression of p21waf1 and p16INK4a., (2) that of p21waf1, p73 and p63 mRNAs; (3) genomic mutations and the loss of heterozygosity of p73 and p53; and (4) frequency of methylation in the 5′CpG promoter region of p16INK4a. Results: In HCCs compared with the adjacent non-cancerous liver tissues, the expression of p21waf1 and p16INK4a was reduced. Indeed, p21waf1 was not detected in 36% (8/22) of HCCs in spite of the presence of p21waf1 mRNA: among them, mutations of p53 gene were found in 50%, whereas a lack of p16INK4a expression in all of them. p21waf1 and p16INK4a were reduced in proportion to the degree of methylation in p16INK4a gene. p73 did not mutated, and p63 did not expressed in HCCs. Conclusion: Methylation status of p16INK4a gene will play a part for reducing constitutive expression of p16INK4a and of p21waf1 coordinately in HCCs.
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