Despite the considerable progress in understanding the molecular
pathology of carcinogenesis, the genetic mechanisms underlying the
development and progression of gallbladder cancer (GC) are poorly
understood. The survival of GC patients is generally poor. Therefore, it
is very useful to define valuable prognostic factors. The most
extensively studied oncogenes in gallbladder carcinogenesis are ras,
commonly mutated in neoplasms of the gastrointestinal tract. K-ras
oncogene is altered in a subset of gallbladder patients and mainly in
those having anomalous junction of the pancreaticobiliary tract. Most of
the studies of genetic abnormalities in GC have focused on p53 gene. p53
mutation/overexpression and/or LOH is present in more than 50% of
gallbladder carcinomas, suggesting an important role in their
pathogenesis. However, these results have not any predictive value yet.
Moreover, the involvement of an alternative molecular pathway, that of
microsatellite instability (MSI), is found in a limited group of GC
patients. Additional research is necessary to establish its possible
relation to defects of the mismatch repair (MMR) system and its proposed
prognostic significance. Further elucidation of the molecular events
specific to GC will help to identify novel molecular targets for the
diagnosis and clinical management of the patients