Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Abstract

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs. Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct's largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations. Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2-8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2-5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323). The incidence of K-ras mutation may be associated with the hypersecretion of mucin.