Significance of Microsatellite Instability and Gene Methylation as Prognostic Biomarkers during Gallbladder Cancer Progression: A Review

Abstract

Gallbladder cancer is a common malignancy of the biliary tract with increasing incidences seen in Chile and Northern India. The disease is aggressive with poor prognosis and a median survival rate of less than 6 months following diagnosis. The aetiology of the tumour is complex with early lymph node metastasis and direct invasion into the liver and peritoneal cavity. Diagnosis is usually incidental during pathological review of cholecystectomy due to non-specific symptoms. Chemotherapy has no significant impact on gallbladder carcinoma as seen in other solid gastrointestinal malignancies. Various pre-disposing factors underlie the progression towards gallbladder cancer, but a strong correlation exists with chronic cholelithtiasis and inflammation. A number of molecular alterations have been reported during gallbladder disease progression which may be associated with prognosis and certain risk factors. But the mechanisms contributing to gallbladder cancer are poorly understood. Various studies report the importance of DNA methylation and microsatellite instability in pathogenesis of gallbladder carcinogenesis. Their involvement in cell cycle pathways and DNA repair mechanisms respectively could make them potential candidates for biomarkers in early detection, diagnosis and therapeutics. Further elucidation of molecular and pathological events during gallbladder disease progression would help to identify novel targets for diagnosis and disease management. This review summarizes significant data related to microsatellite instability and specific gene methylation patterns, and concludes their importance as possible molecular markers of gallbladder cancer.