P16 and p53 gene alterations and accumulations in the malignant evolution of intraductal papillary-mucinous tumors of the pancreas.

Abstract

In general, intraductal papillary-mucinous tumors of the pancreas have a favorable prognosis. However, some invasive carcinomas show a rapid progression and a poor prognosis, such as invasive ductal carcinomas of the pancreas. The aim of this study was to clarify the genetic backgrounds underlying the evolution necessary for these tumors to become invasive carcinomas. Twenty-three patients with intraductal papillary-mucinous tumors, including 9 adenomas, 5 borderline tumors, 3 noninvasive carcinomas, and 6 invasive carcinomas, along with 24 patients with invasive ductal carcinomas were studied. After microdissection, K- ras mutation and loss of heterozygosity (LOH) of the p16 and p53 genes were investigated. In the intraductal papillary-mucinous tumors, K- ras mutations were frequently seen, without a relationship to histological grade. LOH of the p16 gene was observed increasingly with increasing degrees of histological atypia. LOH of the p53 gene was seen only in invasive carcinomas. The frequency of each genetic alteration in invasive carcinomas was the same as that in invasive ductal carcinomas. The accumulation of genetic alterations was as common in invasive carcinomas, as they were in invasive ductal carcinomas. The p16 and p53 gene alterations and accumulations observed are crucial events during the carcinogenesis and malignant progression of intraductal papillary-mucinous tumors of the pancreas.