Detection of K-ras and p53 Gene Mutations in Pancreatic Juice for the Diagnosis of Intraductal Papillary Mucinous Tumors

Abstract

The aim of this study was to investigate mutations of the K-ras oncogene and the p53 tumor suppressor gene in pancreatic juice and to evaluate our method for the diagnosis of intraductal papillary rnucinous tumors (IPMT). Pancreatic juice was collected endoscopically from 12 patients with IPMT who underwent surgical resection (eight carcinomas and four adenomas) and eight cases without evident pancreatic diseases. DNA was extracted and both genes were examined by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. In addition, surgically resected specimens were analyzed for both genes by the same methods, and p53 overexpression was investigated immunohistochernically. K-ras point mutations were detected in pancreatic juice from all 12 patients (loo%) and p53 mutations were detected in five of 12 (42%). They were detected not only in carcinoma but also in adenoma and there was no difference between the mutations detected in pancreatic juice and surgical specimens. No mutations were found in any cases without pancreatic diseases. These findings suggest that alterations of K-ras and p53 gene are common events in the development of IPMT and that genetic analysis of them in pancreatic juice can be a useful tool for the clinical diagnosis of IPMT before surgery.

Multicenter Analysis of Clinicopathologic Features of Intraductal Papillary Mucinous Tumor of the Pancreas: Is It Possible to Predict the Malignancy Before Surgery?

“…11,12 Recently some reports have encouraged the establishment of molecular diagnosis by using K-ras, p53, p16(INK4A), Smad4, telomerase activity, and the expression of MUC1. [13][14][15][16][17][18] However, these techniques are not yet practically useful.…”

Molecular classification of neoplasms of the pancreas

“…IPMNs, particularly high-grade IPMNs, often harbor the same mutations, although at a lower frequency, as are found in invasive ductal adenocarcinomas. These include activating mutations in the KRAS oncogene and inactivating mutations in the TP53 and p16/CDKN2A tumor suppressor genes [2,[54][55][56][57][58][59][60][61][62]. Invasive colloid carcinomas, and the intestinaltype IPMNs from which they usually arise, differ from tubular invasive adenocarcinomas and the pancreatobiliary type IPMNs from which tubular adenocarcinomas can arise in two important ways [50].…”

Intraductal papillary mucinous tumors of the pancreas

“…The degree of papillary formation is important for classification of IPMTs. The papillary structures in the pancreatic ducts range from minimal, comprising only a few cells (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), to an extensive nodular formation in papillary tumors with diameter greater than 1 cm. This classification is represented in the WHO system [2••].…”