K-ras mutations in pancreatic ductal proliferative lesions.

DS Klimstra, DS Longnecker - The American journal of pathology, 1994 - ncbi.nlm.nih.gov
DS Klimstra, DS Longnecker
The American journal of pathology, 1994ncbi.nlm.nih.gov
We read with interest the recent article of DiGiuseppe et a1l regarding the detection of K-ras
mu-tations in the pancreatic ductal epithelium of a patient with a strong family history of
pancreatic adenocarcinoma. The patient did not have an invasive carci-noma anywhere
within the gland, and the K-ras mu-tations were found in a lesion the authors described as"
papillary mucinous duct hyperplasia" without atypia. While the presence of K-ras mutations
in 75% or more of infiltrating pancreatic ductal carcinomas suggests a major role for the K …
We read with interest the recent article of DiGiuseppe et a1l regarding the detection of K-ras mu-tations in the pancreatic ductal epithelium of a patient with a strong family history of pancreatic adenocarcinoma. The patient did not have an invasive carci-noma anywhere within the gland, and the K-ras mu-tations were found in a lesion the authors described as" papillary mucinous duct hyperplasia" without atypia. While the presence of K-ras mutations in 75% or more of infiltrating pancreatic ductal carcinomas suggests a major role for the K-ras oncogene in pancreatic carcinogenesis, the difficulty of studying the human pancreas at early stages in the genesis of carcinoma has limited our knowledge regarding the point at which K-ras mutationsfirst occur. Thefindings of several other investigators2-4 indicate that K-ras mutations may occur before the development of invasive carcinoma and may even precede morphologically clear-cut preneoplastic changes within the ductal epithelium. Yanagisawa et a14 have reported the detection of K-ras mutations in ducts showing papillary hyperplasia in the absence of carcinoma elsewhere within the pancreas. There are significant clinical implications to the detection of K-ras mutations at early stages of ductal proliferation, as it has been proposed to examine pancreatic ductal secretions for the presence of K-ras mutations in patients at risk for the development of carcinoma. If the decision to perform a radical surgical procedure on the basis of K-ras mutations is to be made (especially in the absence of a mass), then the true preneoplastic potential of epithelial proliferative lesions exhibiting these mutations must be well established. Clearly, the finding of K-ras mutations in hyperplasia without atypia is very significant and re-quires replication by other investigators. The report by DiGiuseppe et a1l appears to provide the first in-dependent confirmation of the very early appearance of K-ras mutations reported by Yanagisawa. 4 To assess the point during pancreatic carcinogen-esis at which molecular alterations first occur, it is critical to have reproducible morphological criteria for the proliferative lesions within the ducts, which precede the development of invasive carcinoma. Unfortu-nately, there are few studies characterizing the mor-phological features of preneoplastic ductal lesions. 610 These studies are reported by several groups who have not used standardized terminology for the various lesions. In addition, most studies have examined the changes in residual ducts in the pan-creas surrounding an invasive carcinoma, making it difficult to assess the temporal relationship of putative precursor lesions to invasive carcinoma. Studies evaluating the potential of a given morphologically defined precursor lesion to progress to invasive car-cinoma have not been possible in humans. In a recent study of the ductal proliferative lesions associated with 182 resected ductal adenocarcinomas, Hameed et a11 proposed standardized termi-nology for ductal proliferative lesions, including simple and papillary hyperplasia, atypical hyperpla-sia, and carcinoma in situ, analogous to the termi-nology used for proliferative lesions of the mammary ducts. Ona strictly morphological basis, lesions ex-hibiting only simple or papillary hyperplasia were not regarded as preneoplastic, atypical hyperplasia was felt to be probably preneoplastic, and carcinoma in situ was felt to represent a definite precursor to invasive carcinoma. The lesions illustrated by Yanagi-sawa et al4 would be classified as simple or papillary hyperplasia in this scheme. We believe that the report by DiGiuseppe et a1l illustrates the difficulties inherent in the morphological …
ncbi.nlm.nih.gov