Diagnosis of pancreatic adenocarcinoma by polymerase chain reaction from pancreatic secretions.
As mutations at codon 12 of the Ki-ras oncogene have been shown to occur in 90% of pancreatic adenocarcinomas, a novel strategy for the detection of these mutations in pancreatic secretions obtained at routine endoscopies was developed. Ki-ras DNA was amplified and screened for the presence of mutations at codon 12 with a combination of different rapid, non-radioactive molecular biology techniques. Examination of DNA from cell lines and paraffin-embedded tumour samples was used to establish and test the strategy employed. Pancreatic secretions from 27 patients were examined for the presence of Ki-ras mutations. Mutations at codon 12 were detected in 16/16 secretions from patients with histologically confirmed carcinoma and from one patient with carcinoma of the bile duct. In six patients a mutation identical to the one found in the pancreatic secretions was also demonstrated in paraffin-embedded fine-needle biopsy or surgical samples. Of the remaining ten patients (who had pancreatitis or cholelithiasis) mutations were not found in nine. Ki-ras codon 12 mutation was identified in one of these patients however, and mucous cell hyperplasia of pancreatic ducts was found upon histological examination. These findings establish Ki-ras polymerase chain reaction from pancreatic secretions as a valuable new diagnostic procedure for the demonstration of malignant cells, possibly at an early stage of the disease.
Trümper
L H
LH
Department of Internal Medicine I, University of Saarland at Homburg/Saar, Germany.
Bürger
B
B
von Bonin
F
F
Hintze
A
A
von Blohn
G
G
Pfreundschuh
M
M
Daus
H
H
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D001483:Base Sequence; D002760:Cholangiopancreatography, Endoscopic Retrograde; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics; D004277:DNA, Single-Stranded / Q000032:analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity
D003062:Codon; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded