Molecular diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma is a result of accumulated genetic alterations, including oncogenes such as K-ras, tumor-suppressor genes such as p53, p16 and DPC4 and genome-maintenance genes such as BRCA2, microsatellite instability and telomerase. Recent findings which characterize the molecular genetic profile of the pancreatic cancer have reshaped the nomenclature describing histological progression in pancreatic ductal tumorigenesis. K-ras mutations frequently occur early, whereas changes in the expression and genetic integrity of the p16 gene appear in intermediate lesions, and the inactivation of the p53, DPC4 genes and activation of telomerase occur late in the neoplastic progression. So far K-ras and telomerase activity have been used as molecular markers for the diagnosis of pancreatic carcinoma, whereas p53 and p16 may be a prognostic indicator of pancreatic cancer. Additional tumor-suppressor genes and the related signaling pathway such as ALK-5 are likely to be defined. In addition to the human genome project, these new advances hopefully will accelerate the development of diagnostic and screening techniques for this grave condition.