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Background  To study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma.    Patients and Methods  Out of 36 cases cholangiocarcinoma patients from April 2000 to May 2005 were collected.Promoter hypermethylation of  DAPK ,  p14 ARF  , and  ASC  were detected by methylation-specific PCR on cholangiocarcinoma and normal adjacent tissues samples. Mutation of the p53 gene was examined by automated sequencing. Correlation between methylation of these genes and/or  p53  mutation status with clinical characteristics of patients was investigated by statistical analysis.    Results  We found 66.7% of 36 cholangiocarcinoma patients had methylation of at least one of the tumor suppressor genes analyzed.  p53  gene mutation was found in 22 of 36 patients (61.1%). Combined  p53  mutation and  DAPK, p14 ARF , and/or ASC  methylation was detected in 14 cases (38.9%). There were statistically significant differences in the extent of pathologic biology, differentiation, and invasion between patients with combined  p53  mutation and  DAPK, p14 ARF , and/or ASC  methylation compared to those without (P < 0.05). The survival rate of patients with combined  DAPK, p14 ARF , and ASC  methylation and  p53  mutation was poorer than other patients ( P  < 0.05).    Conclusion  Our study indicates that methylation of  DAPK, p14 ARF , and ASC  in cholangiocarcinoma is a common event. Furthermore,  p53  mutation combined with  DAPK, p14 ARF , and/or ASC  methylation correlates with malignancy and poor prognosis.

Correlation between promoter methylation of p14 ARF , TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma