Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study.
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.
Khalid
Asif
A
Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, USA. khalida@upmc.edu
Zahid
Maliha
M
Finkelstein
Sydney D
SD
LeBlanc
Julia K
JK
Kaushik
Neeraj
N
Ahmad
Nuzhat
N
Brugge
William R
WR
Edmundowicz
Steven A
SA
Hawes
Robert H
RH
McGrath
Kevin M
KM
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
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