Low correspondence between K-ras mutations in pancreatic cancer tissue and detection of K-ras mutations in circulating DNA.
OBJECTIVE
K-ras is the most frequently mutated gene in pancreatic cancer; reported rates range from 70% to 90%. The aim of this study was to evaluate the correspondence between K-ras mutations in pancreatic cancer tissue and in circulating DNA and the value of K-ras mutations as serological marker.


METHODS
The research was conducted in 30 patients with pancreatic cancer in whom both plasma and neoplastic tissues were available. Such research was extended to circulating DNA isolated from 40 patients with chronic pancreatitis. Mutations in codon 12 were examined by mutant allele-specific amplification method and by direct sequencing. Serum values of routinely used tumor markers such as carbohydrate antigen (Ca) 19.9, carcinoembryonic antigen, Ca 50, and Ca 242 have been tested in all the patients enrolled in this study.


RESULTS
K-ras mutations were detected in 70% of neoplastic tissue samples, but no mutated DNA resulted in circulating DNA samples. The 60% of patients with tissue K-ras mutation showed elevation of some tumor markers among Ca 19.9, carcinoembryonic antigen, Ca 50, and Ca 242. As a whole, these last showed low sensitivity (20%-56.67%) and specificity (56.67%-77.5%) when compared with chronic pancreatitis.


CONCLUSIONS
Over the years, there has been no change in the direction of an earlier diagnosis by serological markers, and also, these data indicate that K-ras mutation in serum is an unsatisfactory method for the detection in patients with pancreatic cancer as well as in patients with high risk of progression toward neoplastic pancreatic disease.
FBF S. Pietro Hospital AFaR Research Centre, University of Rome La Sapienza, Rome, Italy. marchese.rodolfo@fbfrm.it
Rodolfo
R
Marchese
Alessandra
A
Muleti
Patrizio
P
Pasqualetti
Barbara
B
Bucci
Antonio
A
Stigliano
Ercole
E
Brunetti
Monica
M
De Angelis
Gianluca
G
Mazzoni
Adriano
A
Tocchi
Stefania
S
Brozzetti
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood; D002908:Chronic Disease; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D003937:Diagnosis, Differential; D018450:Disease Progression; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D015689:Oncogene Protein p21(ras)