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Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study.
- Source :
-
Gastrointestinal endoscopy [Gastrointest Endosc] 2009 May; Vol. 69 (6), pp. 1095-102. Date of Electronic Publication: 2009 Jan 18. - Publication Year :
- 2009
-
Abstract
- Background: The role of pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts remains unclear.<br />Objective: Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cysts.<br />Design: Prospective, multicenter study.<br />Patients: Patients with pancreatic cysts presenting for EUS evaluation.<br />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 loss analysis, mutational amplitude, and sequence determination.<br />Main Outcome Measurements: Cyst fluid analysis compared with surgical pathologic or malignant cytologic examination.<br />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.<br />Limitations: Limited follow-up, selection bias.<br />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.
- Subjects :
- Adenocarcinoma, Mucinous genetics
Adenocarcinoma, Mucinous pathology
Adenocarcinoma, Mucinous surgery
Adenocarcinoma, Papillary genetics
Adenocarcinoma, Papillary pathology
Adenocarcinoma, Papillary surgery
Aged
Biomarkers, Tumor blood
Carcinoembryonic Antigen blood
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal pathology
Carcinoma, Pancreatic Ductal surgery
Cell Transformation, Neoplastic genetics
Cell Transformation, Neoplastic pathology
Cyst Fluid metabolism
Cystadenocarcinoma, Mucinous genetics
Cystadenocarcinoma, Mucinous pathology
Cystadenocarcinoma, Mucinous surgery
Cystadenoma, Mucinous genetics
Cystadenoma, Mucinous pathology
Cystadenoma, Mucinous surgery
Diagnosis, Differential
Female
Humans
Male
Middle Aged
Pancreas pathology
Pancreatic Cyst pathology
Pancreatic Cyst surgery
Pancreatic Neoplasms pathology
Pancreatic Neoplasms surgery
Precancerous Conditions pathology
Precancerous Conditions surgery
Prognosis
Prospective Studies
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins p21(ras)
ras Proteins genetics
DNA, Neoplasm genetics
Loss of Heterozygosity genetics
Pancreatic Cyst genetics
Pancreatic Neoplasms genetics
Precancerous Conditions genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6779
- Volume :
- 69
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Gastrointestinal endoscopy
- Publication Type :
- Academic Journal
- Accession number :
- 19152896
- Full Text :
- https://doi.org/10.1016/j.gie.2008.07.033