title: Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.
abstract: OBJECTIVE
  Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer.
  
  
  METHODS
  We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls.
  
  
  RESULTS
  TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions.
  
  
  CONCLUSIONS
  We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.
authors.affiliation: Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sadakari
authors.forename: Michael
authors.initials: M
authors.lastname: Borges
authors.forename: Mark
authors.initials: M
authors.lastname: Topazian
authors.forename: James
authors.initials: J
authors.lastname: Farrell
authors.forename: Sapna
authors.initials: S
authors.lastname: Syngal
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lee
authors.forename: Ihab
authors.initials: I
authors.lastname: Kamel
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Lennon
authors.forename: Spencer
authors.initials: S
authors.lastname: Knight
authors.forename: Sho
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Marcia Irene
authors.initials: MI
authors.lastname: Canto
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D010189:Pancreatic Juice / Q000166:cytology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000175:diagnosis*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53