DNA Methylation Alterations in the Pancreatic Juice of Patients with Suspected Pancreatic Disease

• Hiroyuki Matsubayashi

  1Pathology, Departments of

• Marcia Canto

  2Medicine,

• Norihiro Sato

  1Pathology, Departments of

• Alison Klein

  1Pathology, Departments of

• Tadayoshi Abe

  1Pathology, Departments of

• Keishi Yamashita

  5Otolaryngology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland; and

• Charles J. Yeo

  3Surgery,

• Anthony Kalloo

  2Medicine,

• Ralph Hruban

  1Pathology, Departments of

• Michael Goggins

  1Pathology, Departments of

Abstract

Molecular markers of pancreatic neoplasia could aid in the evaluation of visible pancreatic lesions and indicate neoplasia invisible to imaging. We evaluated methylation-specific PCR (MSP) assays that detect aberrantly methylated DNA for their use as markers of pancreatic neoplasia. Methylation analysis was done on pancreatic juice collected endoscopically or surgically from 155 individuals with suspected pancreatic disease: 56 patients had pancreatic ductal adenocarcinoma, 17 had intraductal papillary mucinous neoplasms, 26 had symptomatic chronic pancreatitis, 12 controls lacked evidence of pancreatic disease, and 44 were asymptomatic individuals at increased risk of developing familial pancreatic cancer undergoing screening for pancreatic neoplasia. Pancreatic juice DNA was analyzed for promoter methylation using conventional MSP assays for 17 genes. For six genes, pancreatic juice methylation was quantified using real-time quantitative MSP (QMSP; Cyclin D2, FOXE1, NPTX2, ppENK, p16, and TFPI2). Quantifying pancreatic juice methylation using QMSP with a cutoff of >1% methylated DNA could better predict pancreatic cancer than detecting methylation using conventional MSP. In the endoscopic group, 9 of 11 patients with pancreatic cancer, but none of 64 individuals without neoplasia had ≥1% methylation for two or more of the best five QMSP assays (82% sensitivity and 100% specificity; P < 0.0001). The prevalence of pancreatic juice methylation in patients with chronic pancreatitis was less than in patients with pancreatic cancer but higher than in controls and similar to high-risk individuals. The detection and quantification of aberrantly methylated DNA in pancreatic juice is a promising approach to the diagnosis of pancreatic cancer. (Cancer Res 2006; 66(2): 1208-17)

Journal

• Cancer Research

  Cancer Research 66 (2), 1208-1217, 2006-01-15

  American Association for Cancer Research (AACR)

Keywords

• Cancer Research
• Oncology

Details

• CRID: 1360574095934366080
• NII Article ID: 30018587737
• DOI: 10.1158/0008-5472.can-05-2664
• ISSN: 15387445
• ISSN: 00085472
• Web Site: https://aacrjournals.org/cancerres/article-pdf/66/2/1208/2554521/1208.pdf
• Data Source:
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  • CiNii Articles