[摘要]：Despite the progress of therapy, outcomes of advanced hepatoblastoma patients who are refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the mortality rate, novel prognostic markers are needed for better therapy planning. We examined the methylation status of 13 candidate tumor suppressor genes in 20 hepatoblastoma tumors by conventional methylation-specific PCR (MSP) and found hypermethylation in 3 of the 13 genes. We analyzed the methylation status of these 3 genes (RASSFIA, SOCS1 and CASP8) in 97 tumors and found hypermethylation in 30.9, 33.0 and 15.5%, respectively. Univariate analysis showed that only the methylation status of RASSFIA but not the other 2 genes predicted the outcome, and multivariate analysis showed a weak contribution of RASSFIA methylation to overall survival. Using quantitative MSP, we found RASSFIA methylation in 44.3% of the 97 tumors. CTNNB1 mutation was detected in 67.0% of the 97 tumors. While univariate analysis demonstrated RASSFIA methylation, CTNNB1 mutation and other clinicopathological variables as prognostic factors, multivariate analysis identified RASSFIA methylation (p = 0.043; relative risk 9.39) and the disease stage (p = 0.002; relative risk 7.67) but not CTNNB1 mutation as independent prognostic factors. In survival analysis of 33 patients in stage 313 or 4, patients with unmethylated tumor had better overall survival than those with methylated tumor (p = 0.035). RASSFIA methylation may be a promising moleculargenetic marker to predict the treatment outcome and may be used to stratify patients when clinical trials are carried out. (C) 2008 Wiley-Liss, Inc.
