Follow-up study of K-ras mutations in the plasma of patients with pancreatic cancer: correlation with clinical features and carbohydrate antigen 19-9

Pancreas. 2009 Jul;38(5):534-41. doi: 10.1097/MPA.0b013e31819f6376.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

MeSH terms

  • CA-19-9 Antigen / blood*
  • Cell Line, Tumor
  • DNA / blood
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genes, ras / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Polymerase Chain Reaction
  • Prognosis
  • Survival Analysis

Substances

  • CA-19-9 Antigen
  • DNA