Detection of point mutations in the K-ras oncogene at codon 12 in pure pancreatic juice for diagnosis of pancreatic carcinoma

Abstract
Background. Mutations in the K‐ras oncogene at codon 12 are detected at a remarkably high frequency in pancreatic carcinomas and are believed to be a critical event in oncogenesis. The authors attempted to detect K‐ras mutations in DNA obtained from pure pancreatic juice collected endoscopically, as a novel diagnostic approach to pancreatic carcinoma. Methods. K‐ras mutations were examined using the two‐step polymerase chain reaction (PCR) combined with restriction enzyme digestion, followed by nonra‐dioisotopic single‐strand conformation polymorphism (SSCP) analysis. Results. Specific mutations of the K‐ras gene at codon 12 were found in six of nine (67%) duct cell carcinomas, all of which were negative by cytodiagnosis of the same pure pancreatic juice. K‐ras mutations were not detected in the pancreatic juice from 14 healthy control subjects, 10 patients with chronic pancreatitis, or 3 patients with islet cell tumors. Conclusions. Detection of K‐ras mutation at codon 12 in pancreatic juice is highly specific for diagnosing pancreatic duct cell carcinoma and may be a valuable diagnostic modality for pancreatic carcinoma and for differentiating chronic pancreatitis from carcinoma. Cancer 1994; 73:1589–94.