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 carci noma. Several ras mutations are consistently detected in the pancreatic jui ce from patients with chronic pancreatitis. The p53 gene mutations have bee n detected occasionally in chronic pancreatitis tissue. It was the aim of t his 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 pancre atitis 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 grad ient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/poly merase 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 durat ion of pancreatitis or drinking habits was found, K-ras mutations correlate d with both heavy smoking and severity of the disease. Conclusion: p53 and ras mutations can be detected in a minority of pancreat ic juice samples from patients with chronic pancreatitis in the absence of malignancy.