Follow-Up Study of K-ras Mutations in the Plasma of Patients With Pancreatic Cancer

Abstract

We followed up the presence of Kirsten rat sarcoma (K-ras) mutations in plasma DNA and assessed its clinical value in patients with pancreatic cancer. Plasma samples (N = 430) of 56 patients with pancreatic cancer and 13 patients with pancreatitis were analyzed by real-time polymerase chain reaction using peptide nucleic acid-mediated polymerase chain reaction clamping. K-ras mutations could be detected in the plasma DNA of 20 patients with cancer (36%). No K-ras mutation was found in the plasma of patients with pancreatitis. In 7 (35%) of 20 patients with lowly or moderately elevated carbohydrate antigen 19.9 (CA 19-9) levels lower than 100 U/mL, the result of the assay was positive for K-ras mutation. The combination of K-ras and CA 19-9 level determination gave a sensitivity for the diagnosis of pancreatic cancer of 91% (40/44) of the patients. Thirteen of 35 patients with pancreatic cancer (102 plasma samples) with elevated CA 19-9 levels (>35 U/mL) and altered K-ras gene showed significant correlation with elevated CA 19-9 levels (P=0.048). The summary of our approach of noninvasive, convenient, extremely high-sensitive K-ras mutation analysis in plasma might provide diagnostic and prognostic information to clinicians but will not be sufficient in a standardized early diagnosis of pancreatic carcinoma. The combination with CA 19-9 assay is useful for detection and prognostic evaluation of pancreatic carcinoma.