DETECTION OF K-RAS GENE-MUTATIONS AT CODON-12 IN THE PANCREATIC-JUICEOF PATIENTS WITH INTRADUCTAL PAPILLARY MUCINOUS TUMORS OF THE PANCREAS

BACKGROUND. The authors previously found specific mutations of the K-r as gene at codon 12 in the pancreatic juice of 67% of patients (6 of 9 ) with pancreatic ductal carcinoma, and the detection of these mutatio ns was useful for diagnosis. This study was performed to detect and ev aluate K-ras mutations in pancreatic juice from patients with intraduc tal papillary mucinous tumor of the pancreas, which is considered a lo w grade malignancy. The results were interpreted from the viewpoint of clinical significance. METHODS. K-ras mutations were examined using s eminested polymerase chain reaction analysis combined with restriction enzyme digestion, followed by nonradioisotopic single strand DNA conf ormation polymorphism. RESULTS. Twelve of thirteen cases (92%) of intr aductal papillary mucinous tumor of the pancreas, confirmed histologic ally (9 adenomas and 4 carcinomas), and 26 of 43 cases (60%) of ductal carcinoma showed specific K-ras gene mutations in the pancreatic juic e. Furthermore, 4 of 22 patients (18%) with chronic pancreatitis, foll owed for more than 1 year without a sign of pancreatic tumor, showed K -ras mutations. In contrast, no mutations of the K-ras gene were detec ted in the pancreatic juice from 28 normal controls. CONCLUSIONS. K-ra s mutations were found in the pancreatic juice of all but one patient with intraductal papillary mucinous tumor of the pancreas, but they we re not useful for distinguishing carcinoma from adenoma. The authors c oncluded that K-ras mutations are not a specific marker for pancreatic neoplasms because similar mutations were detected in the pancreatic j uice from patients with chronic pancreatitis. At the present time, the detection of K-ras mutations in pancreatic juice should be used clini cally as an adjunct diagnostic modality for pancreatic diseases. (C) 1 997 American Cancer Society.