Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer.
OBJECTIVE
To develop an early diagnostic test for pancreatic cancer based on the identification of K-ras mutations in pure pancreatic juice collected during endoscopic retrograde pancreatography.


METHODS
Prospective study with masked comparison. The standard criteria for the diagnosis of pancreatic cancer were pancreatography or surgery (or both) and histopathology, with follow-up ranging from 6 to 40 months.


METHODS
Referral center.


METHODS
24 patients with no pancreatic disease (group 1); 29 patients with nontumoral pancreatic disease (group 2); and 22 patients with pancreatic tumor (group 3). Endoscopic ductal aspiration of cells or brush cytology was done on patients having endoscopic retrograde pancreatography for diagnostic or therapeutic reasons.


METHODS
Confirmation of mutation rates in patients with pancreatic cancer.


RESULTS
K-ras gene analysis was done by polymerase chain reaction-mediated restriction fragment length polymorphism analysis and direct sequencing. All patients from groups 1 and 2 (n = 53) had a normal sequence for the K-ras 12th codon (group 1, 0% [95% CI, 0% to 14%]; group 2, 0% [CI, 0% to 12%]). Mutations were seen in 17 of the 22 patients in group 3 (77% [CI, 55% to 92%]). Two of the 17 had no evidence of pancreatic cancer when K-ras was first studied. One had chronic abdominal pain and the other presented with acute pancreatitis. Both were initially free of any pancreatic mass, but they developed tumors 18 and 40 months, respectively, after the K-ras mutations were identified.


CONCLUSIONS
Identification of K-ras mutations in samples of pancreatic juice may be useful in differentiating between pancreatic cancer and noncancerous pancreatic diseases. K-ras mutation can precede clinical evidence of pancreatic cancer, but the clinical implications of this finding need further study.
Berthélemy
P
P
Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
Bouisson
M
M
Escourrou
J
J
Vaysse
N
N
Rumeau
J L
JL
Pradayrol
L
L
D003937:Diagnosis, Differential; D004311:Double-Blind Method; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D010182:Pancreatic Diseases / Q000235:genetics; D010189:Pancreatic Juice / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011446:Prospective Studies