title: Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study.
abstract: BACKGROUND
  The role of pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts remains unclear.
  
  
  OBJECTIVE
  Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cysts.
  
  
  METHODS
  Prospective, multicenter study.
  
  
  METHODS
  Patients with pancreatic cysts presenting for EUS evaluation.
  
  
  METHODS
  EUS-guided pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA) level determination, and a detailed DNA analysis; incorporating DNA quantification, k-ras mutation and multiple allelic loss analysis, mutational amplitude, and sequence determination.
  
  
  METHODS
  Cyst fluid analysis compared with surgical pathologic or malignant cytologic examination.
  
  
  RESULTS
  The study cohort consisted of 113 patients with 40 malignant, 48 premalignant, and 25 benign cysts. Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver-operator characteristic curve analysis indicated optimal cutoff points for allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and CEA (AUC 0.74; optimal value >148 ng/mL). Components of DNA analysis detecting malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA amount (optical density ratio >10, AUC 0.79). The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy. All malignant cysts with negative cytologic evaluation (10/40) could be diagnosed as malignant by using DNA analysis.
  
  
  CONCLUSIONS
  Limited follow-up, selection bias.
  
  
  CONCLUSIONS
  Elevated amounts of pancreatic cyst fluid DNA, high-amplitude mutations, and specific mutation acquisition sequences are indicators of malignancy. The presence of a k-ras mutation is also indicative of a mucinous cyst. DNA analysis should be considered when cyst cytologic examination is negative for malignancy.
authors.affiliation: Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, USA. khalida@upmc.edu
authors.forename: Asif
authors.initials: A
authors.lastname: Khalid
authors.forename: Maliha
authors.initials: M
authors.lastname: Zahid
authors.forename: Sydney D
authors.initials: SD
authors.lastname: Finkelstein
authors.forename: Julia K
authors.initials: JK
authors.lastname: LeBlanc
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kaushik
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Ahmad
authors.forename: William R
authors.initials: WR
authors.lastname: Brugge
authors.forename: Steven A
authors.initials: SA
authors.lastname: Edmundowicz
authors.forename: Robert H
authors.initials: RH
authors.lastname: Hawes
authors.forename: Kevin M
authors.initials: KM
authors.lastname: McGrath
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D020420:Cyst Fluid / Q000378:metabolism; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology / Q000601:surgery; D018291:Cystadenoma, Mucinous / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology; D010181:Pancreatic Cyst / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins