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.