title: A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer.
abstract: OBJECTIVE
  Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC.
  
  
  METHODS
  Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland.
  
  
  RESULTS
  We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%).
  
  
  CONCLUSIONS
  We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: Asuragen, Inc, Austin, Texas.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Adai
authors.affiliation: Department of Pathology and Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.affiliation: Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Sherbrooke, Fleurimont, Quebec, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Rateb
authors.affiliation: Department of Pathology and Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Vignesh
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Sherbrooke, Fleurimont, Quebec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Menard
authors.affiliation: Department of Endoscopy, Hospital of the Ministry of Internal Affairs and Administration, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiechowska-Kozłowska
authors.affiliation: Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Bołdys
authors.affiliation: Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Hartleb
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Sanders
authors.affiliation: Institute of Pathology, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Johanna B
authors.initials: JB
authors.lastname: Munding
authors.affiliation: Institute of Pathology, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Molecular GI-Oncology and Department of Pathology, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.affiliation: Department of Medicine, Division of Radiology, Medical University of Łódź, Łódz, Poland.
authors.forename: Ludomir
authors.initials: L
authors.lastname: Stefańczyk
authors.affiliation: Department of Pathology and Department of Gasteroenterology and Hepatology, Dartmouth Hitchcock Medical Center and The Audrey and Theodor Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: David C
authors.initials: DC
authors.lastname: Whitcomb
authors.affiliation: Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Darwin L
authors.initials: DL
authors.lastname: Conwell
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Sherbrooke, Fleurimont, Quebec, Canada.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Morisset
authors.affiliation: Department of Pathology and Department of Gasteroenterology and Hepatology, Dartmouth Hitchcock Medical Center and The Audrey and Theodor Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Gardner
authors.affiliation: Department of Pathology and Department of Gasteroenterology and Hepatology, Dartmouth Hitchcock Medical Center and The Audrey and Theodor Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Gordon
authors.affiliation: Department of Pathology and Department of Gasteroenterology and Hepatology, Dartmouth Hitchcock Medical Center and The Audrey and Theodor Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.affiliation: Asuragen, Inc, Austin, Texas.
authors.forename: Maura B
authors.initials: MB
authors.lastname: Lloyd
authors.affiliation: Asuragen, Inc, Austin, Texas.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wylie
authors.affiliation: Asuragen, Inc, Austin, Texas.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Labourier
authors.affiliation: Asuragen, Inc, Austin, Texas.
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Andruss
authors.affiliation: Asuragen, Inc, Austin, Texas. Electronic address: aschwarzbach@asuragen.com.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Szafranska-Schwarzbach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle / Q000379:methods*; D002170:Canada; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis*; D003584:Cytological Techniques / Q000379:methods*; D019160:Endosonography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D011044:Poland; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D014481:United States; D055815:Young Adult
chemical_list: D035683:MicroRNAs
keywords: Cytologic Diagnosis; Fine-Needle Aspirate; MicroRNA; Pancreatic Cancer