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

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.