Follow-up study of K-ras mutations in the plasma of patients with pancreatic cancer: correlation with clinical features and carbohydrate antigen 19-9.
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.
Däbritz
Jan
J
Department of Medical Oncology and Hematology, Charité School of Medicine, Campus Virchow-Klinikum, Humboldt University of Berlin, Berlin, Germany. Jan.Daebritz@charite.de
Preston
Roman
R
Hänfler
Joachim
J
Oettle
Helmut
H
D018395:CA-19-9 Antigen / Q000097:blood*; D045744:Cell Line, Tumor; D004247:DNA / Q000097:blood / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis
D018395:CA-19-9 Antigen; D004247:DNA