[Genetic profile and molecular bases of pancreatic carcinogenesis]

The possibility that carcinogenesis is a multiphasic process has been well demonstrated in colorectal cancer, at least in cancers arising from a benign adenomatous polyp. However, because of the difficulty of performing histopathological studies of the pancreas, the multiphasic nature of carcinogenesis is proving more difficult to demonstrate in pancreatic ductal adenocarcinoma (d-ADC), although a series of findings, reviewed in the present article, strongly support this characteristic. Firstly, d-ADC shows a fairly exclusive genetic-molecular profile, found in 70% of cases; this profile consists of the association of the K-ras oncogene and inactivation of the tumor suppressor genes p16, p53 and DPC4. Secondly, a series of lesions in the ductal epithelium, in healthy pancreatic tissue close to a d-ADC, have been identified, which seem to represent precancerous histopathological stages. Lastly, there is the suspicion that the mutations defining this genetic-molecular profile appear gradually, in a certain sequence, throughout the stages of progression. Most probably, rather than the order of appearance, the accumulation of these genetic-molecular events are what prompt quiescent ductal epithelium to progress to mitogenic cellular hyperplasia, leading to irreversible mutagenic cellular dysplasia.