Ki-ras oncogene mutations in chronic pancreatitis: which discriminating ability for malignant potential?

Ki-ras mutations are found in the majority of pancreatic adenocarcinomas (85-100%). Ki-ras analysis was increasingly used in ERCP samples in order to differentiate between chronic pancreatitis and pancreatic cancer. However, its sensitivity was recently reported to be low due to a high prevalence of ras mutations in patients with chronic pancreatitis (25-37%). Detection of Ki-ras mutations in microdissected pancreata confirmed their high frequency (55-83%) in pancreatic intraductal lesions (PILs) observed in chronic pancreatitis specimens and in the vicinity of invasive pancreatic carcinoma. There is now molecular evidence that PILs can be precursors of invasive carcinoma, since they can harbor genetic alterations identical to those of the adjacent carcinoma. Similarly, we observed 2 patients with chronic pancreatitis who developed pancreatic cancer 18 and 24 months after the evidence of Ki-ras mutations in pancreatic brushings. However, besides these findings, ras mutations were also identified in nondiseased pancreata coming from autopsy series. The current data on ras analysis in pancreatic juice and brushings or in microdissected pancreata suggest that PILs with Ki-ras mutations do not inevitably lead toward invasive carcinoma. Ki-ras mutations probably have a low discriminating ability for malignant potential and their detection in pancreatic juice is not justified routinely for differentiating between benign and malignant pancreatic diseases. However, prospective follow-up of patients with chronic pancreatitis harboring a mutant ras is probably of major interest by combining the search for other genetic markers that have the ability to characterize patients with the greater risk of malignant transformation.