K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas

Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique tumor that is composed of tumor cells with different cell atypia. K-ras and p53 alterations have been shown to occur in pancreatic duct cell carcinoma (PDC), but they have not been well documented in the individual lesion of IMHN. The aim of this study was to examine the relation of the genetic alterations of K-ras and p53 in IMHN to the tumorigenesis of the pancreas. In 32 microscopically dissected lesions of seven cases of IMHN, the K-ras mutation was investigated by primer-mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism. Mutant p53 expression was examined in the adjacent serial sections by immunohistochemistry. In IMHN, alterations of K-ras and p53 were frequently observed (71.9 and 50%, respectively). The frequency became higher as the grade of cell atypia increased. Simultaneous alterations of the two genes were detected in carcinoma and its accompanying hyperplastic and dysplastic lesions. It is suggested that alterations of K-ras and p53 may be early events in the tumorigenesis of IMHN and may cooperate to produce neoplastic transformation of the pancreatic duct epithelium.