The role of p21(ras) in pancreatic neoplasia and chronic pancreatitis

K-ras mutations have been detected in both ductal cell carcinoma and intrad uctal papillary mucinous tumor (IPMT) of pancreas. The frequency of this mu tation in ductal cell carcinoma is high, whereas in IPMT, it is variable. I t has been suggested that the relatively high frequency of this mutation in ductal cell carcinomas compared with IPMT may account for the differences in biological behavior between these tumor types. More recently, the signif icance of K-ras mutations in pancreatic tissue has been questioned with the demonstration of this mutation in nonneoplastic pancreata. The current stu dy aims to estimate the relative frequency and evaluate the biological sign ificance of K-ras gene mutations in these neoplasms by performing polymeras e chain reaction (PCR) assays of microdissected areas of IPMT, ductal cell carcinomas, and resected chronic pancreatitis. The study also investigates whether alterations of p21(ras) occur in K-ras mutation-negative cases by u sing immunohistochemical staining for K-, N- and H-ras. K-ras codon 12 muta tions were found almost as frequently in IPMT (71%) as in ductal cell carci nomas (78%). They were also associated with the earliest morphological lesi on, flat mucinous change. This mutation also was detected in 42% of cases o f chronic pancreatitis. Expression of p21(ras) was found to correlate close ly with K-ras mutation status in IPMT and ductal cell carcinoma. Negative s taining for pan-ras, II-ras, and N-ras in cases with wild-type K-ras genes suggests that alternative routes of ras gene alteration are not operative i n IPMT or ductal carcinoma. The findings suggest that K-ras activation is f requently associated with both IPMT and ductal cell carcinoma. Its high pre valence in nonneoplastic pancreata suggests that it is also associated with self-limited morphological lesions of the pancreas that do not progress to malignancy. Copyright (C) 1999 by W.B. Saunders Company.