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 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 cyst. Design: Prospective, multicenter study. Patients: Patients with pancreatic cysts presenting for EUS evaluation. Intervention: 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 has analysis, mutational amplitude, and sequence determination. Main Outcome Measurements: 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 cyst 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 cytology evaluation (10/40) could be diagnosed as malignant by using DNA analysis. Limitations: United follow-up, selection bias. Conclusions: Elevated amounts of pancreatic cyst fluid DNA hi,high-amplitude mutations, Mid specific mutation acquistion sequences we 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. (Gastrointest Endosc 2009;69:1095-102.)