K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: Diagnostic utility and prognostic significance

Purpose: Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnost ic utility and the prognostic significance of this finding have never been addressed, Patients and Methods: Forty-four consecutive patients with histologically c onfirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumo rs of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included, Plasma DNA was isolated and K-ras cod on-12 mutations were analyzed by means of restriction fragment length polym orphism-polymerase chain reaction and single-strand conformation polymorphi sm techniques. Patients were followed up to establish their clinical outcom e. Results: The mutant-type K-ras gene was found in plasma DNA samples of 12 ( 27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant me tastases (P = .02). In addition, K-ras mutations were detected in the plasm a DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset o f patients with pancreatic masses, the sensitivity and specificity of plasm a K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectiv ely. Finally, pancreatic carcinoma patients with the mutant-type K-ros gene in plasma DNA exhibited a shorter survival time than patients with the wil d-type gene (P < .005), and plasma K-ras mutations were identified as the o nly independent prognostic factor (odds ratio, 1.51; 95% confidence interva l, 1.02 to 2.23). Conclusion: Plasma K-ras analysis is a highly specific, low-sensitivity app roach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma. (C) 1999 by American Society of Clinical Oncolog y.