Promoter methylation profile in preneoplastic and neoplastic gallbladder lesions

Gallbladder carcinoma (GBC) is a highly malignant neoplasm and represents the leading cause of cancer death in Chilean women. In order to determine the potential role of promoter methylation in gallbladder carcinogenesis, we investigated the frequency of this epigenetic mechanism by methylation-specific polymerase chain reaction (MSP) in 35 chronic cholecystitis (CC, separated according to the presence or absence of metaplasia), 19 early cancers (mucosa or muscularis propia invasion) and 48 advanced carcinomas with invasion of the gallbladder subserosa (25 cases) and serosa (23 cases). We examined 14 genes and observed an increase of multigenic methylation during tumoral progression which was not significantly associated with the patient's age. Four genes (DAPK1, DLC1, TIMP3, and RARbeta2) displayed a progressive increase in their methylation status from CC without metaplasia to advanced carcinoma invading the serosa layer (P