title: A combination of molecular markers and clinical features improve the classification of pancreatic cysts.
abstract: OBJECTIVE
  The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients.
  
  
  METHODS
  We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers.
  
  
  RESULTS
  We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%.
  
  
  CONCLUSIONS
  We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.
authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: David L
authors.initials: DL
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: Department of Biostatistics and Bioinformatics, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: Department of Radiology, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: ARC-Net Research Centre, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology, General Surgery B, University and Hospital Trust of Verona, Verona, Italy.
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authors.affiliation: Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
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authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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authors.affiliation: Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
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authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Luis A
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
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authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Rachel
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authors.lastname: Karchin
authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Bert
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authors.lastname: Vogelstein
authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University, Baltimore, Maryland. Electronic address: amlennon@jhmi.edu.
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mesh_terms: D000328:Adult; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010179:Pancreas / Q000473:pathology*; D010181:Pancreatic Cyst / Q000145:classification* / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: Diagnosis; IPMN; Molecular; Pancreatic Cyst