Diagnosing pancreatic cancer using methylation specific PCR analysis of pancreatic juice

Noriyoshi Fukushima, Kimberly M. Walter, Takashi Ueki, Norihiro Sato, Hiroyuki Matsubayashi, John L. Cameron, Ralph H. Hruban, Marcia Canto, Charles J. Yeo, Michael Goggins

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to determine the utility of detecting methylated ppENK and p16 in pancreatic juice by methylation specific PCR as a marker of pancreatic adenocarcinoma. Pancreatic juice samples were collected either intraoperatively, from 92 patients undergoing pancreaticoduodenectomy for benign (n=20) and malignant periampullary disease (n = 72) or endoscopically (by duodenal aspiration after secretin infusion), from 13 patients undergoing investigation for pancreatic disease. Methylated ppENK was detected in the pancreatic juice of 30 (66.7%) of 45 patients with pancreatic ductal adenocarcinoma, in 4 (44.4%) of 9 patients with intraductal papillary-mucinous adenocarcinoma, and in 7 (41.2%) of 17 patients with other periampullary carcinomas, using methylation specific PCR. Methylated p16 was detected in a lower percentage of these patients (11.1%, 11.1% and 23.5%, respectively). In contrast, methylated ppENK and p16 were not detected in 20 patients with non-malignant periampullary disease including 12 patients with chronic pancreatitis. Methylated ppENK was detected in 30 of 33 (90.9%) primary pancreatic adenocarcinoma and methylated p16 was in 6/33 (18.2%). Despite the absence of ppENK and p16 methylation in normal pancreas, methylated ppENK and p16 was present in the duodenum of 90.5% and 28.6%, respectively of patients without cancer. Further, methylated ppENK and p16 was seen in 88.9% and 11.1%, respectively of pancreatic juice samples obtained by duodenal aspiration from patients without cancer. We conclude that since ppENK and p16 are not normally methylated in pancreatic secretions, detection of methylated ppENK and p16 in pure pancreatic juice obtained by direct cannulation of the pancreatic duct to avoid duodenal secretions may suggest the presence of pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)78-83
Number of pages6
JournalCancer Biology and Therapy
Volume2
Issue number1
StatePublished - Jan 2003

Keywords

  • Methylation
  • Pancreatic adenocarcinoma
  • Pancreatic juice
  • ppENK

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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