Ko E et al. (2008) Promoter hypermethylation of the p16 gene is associated with poor prognosis in recurrent early-stage hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 17: 2260–2267

Patients with hepatocellular carcinoma (HCC) have a poor prognosis mainly because of high rates of recurrence, for which prognostic factors are lacking. Ko and colleagues assessed the role of promoter hypermethylation of genes expressed in HCC as prognostic factors of recurrence.

The authors used a methylation-specific polymerase chain reaction technique to analyze the methylation status of seven genes in tissue samples from 265 patients with HCC obtained at surgical resection. Recurrence developed in 38% of patients (n = 102). Promoter hypermethylation of p14 (CDK2AP2), p15 (CDKN2B), p16 (CDKN2A), GSTP1, SYK, CDH1 and integrin α4 (ITGA4) genes was detected in 6%, 21%, 67%, 75%, 12%, 57% and 23% of the tissue samples, respectively. After adjustment for confounding factors, no associations were observed between promoter hypermethylation of any gene and risk of recurrence. Overall survival and survival after recurrence of stage I to II HCC were very poor in patients whose tumors did not express the p16 protein; however, concomitant expression of p53 did not worsen their prognosis. Patients with recurrent stage I to II HCC and p16 methylation had significantly worse overall survival than similar patients without p16 methylation (hazard ratio 4.05). Moreover, the risk of treatment failure was approximately 3.80 times higher in patients with recurrent stage I to II HCC and p16 methylation compared with such patients without p16 methylation (P = 0.04).

These results suggest that p16 methylation is associated with poor prognosis after surgery in recurrent, early-stage HCC.