p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis.
BACKGROUND
Mutations in p53 and ras genes are frequent in pancreatic carcinoma. Several ras mutations are consistently detected in the pancreatic juice from patients with chronic pancreatitis. The p53 gene mutations have been detected occasionally in chronic pancreatitis tissue. It was the aim of this study to evaluate the presence and clinical significance of p53 and ras mutations in clinical pancreatic juice samples from patients with chronic pancreatitis.


METHODS
Pancreatic juice was obtained from 66 patients with chronic pancreatitis and no evidence of pancreatic carcinoma (51 men, 15 women; age 17-86 years [mean 49.6 +/- 12.9]). Patients were followed prospectively for 26 +/- 3 (4-54) months. Detection of p53 gene mutations was by temperature gradient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/polymerase chain reaction, restriction fragment length polymorphism/polymerase chain reaction. All mutations were confirmed by sequencing.


RESULTS
Five of 66 (7.5%) pancreatic juice samples contained p53 mutations, and ras mutations were detected in 6 cases (9%). Cytology was negative in all cases. No pancreatic carcinoma developed during follow-up and neither cancer cells nor preneoplastic lesions could be detected histologically in resected specimens. Although no correlation between p53 mutations and duration of pancreatitis or drinking habits was found, K-ras mutations correlated with both heavy smoking and severity of the disease.


CONCLUSIONS
p53 and ras mutations can be detected in a minority of pancreatic juice samples from patients with chronic pancreatitis in the absence of malignancy.
Löhr
M
M
Division of Gastroenterology, Department of Medicine, University of Rostock, Rostock, Germany.
Müller
P
P
Mora
J
J
Brinkmann
B
B
Ostwald
C
C
Farré
A
A
Lluis
F
F
Adam
U
U
Stubbe
J
J
Plath
F
F
Nizze
H
H
Hopt
U T
UT
Barten
M
M
Capellá
G
G
Liebe
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010189:Pancreatic Juice / Q000378:metabolism*; D010195:Pancreatitis / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011336:Probability; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D005819:Genetic Markers