p53 and DPC4 alterations in the bile of patients with pancreatic carcinoma

J Surg Oncol. 2004 Dec 15;88(4):210-6. doi: 10.1002/jso.20151.

Abstract

Introduction: Pancreatic cancer is still predominantly diagnosed in advanced stages, and 85%-90% of patients are not eligible for surgery at diagnosis. This is mainly due to the great difficulty in detecting the tumour at an early stage and presently no satisfactory results have been obtained to overcome this problem. Studies on molecular genetic profile of pancreatic cancer may represent an important approach. This study was focused on the mutations of p53 and DPC4 detectable in the bile of patients with histologically proven pancreatic cancers.

Materials and patients: We analysed specimens of bile collected through percutaneous transhepatic biliary catheters, placed to treat malignant biliary obstruction in 25 patients with pancreatic adenocarcinoma. A percentage of mutation was obtained of 43 % for the microsatellite D17S945 (p53), 54% and 50 % for D18S46 and D18S474 (DPC4), respectively. The percentage of amplification was 67%, 93,6%, and 80%.

Conclusion: We consider the results encouraging enough to decide to enlarge the number of patients examined. The aim is to determine if a test for DPC4 and p53 mutations is eligible for introduction in clinical routine use. More sets of samples are required to satisfactorily answer this question.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / genetics*
  • Bile / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Diagnosis, Differential
  • Humans
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Mutation*
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Smad4 Protein
  • Trans-Activators / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • DNA-Binding Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Tumor Suppressor Protein p53