title: Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology.
abstract: Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2-7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples.
  
  
  
  Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture. Collected samples were frozen at -80 °C. The supernatant was washed and lysed cells incubated with HRP-labelled anti-MCM5 mouse monoclonal antibody. Test positivity was determined by optical density absorbance. Patients underwent biliary brush cytology or additional investigations as per clinical routine.
  
  
  
  Ninety-seven patients were included in the study; 50 had malignant strictures. Median age was 65 years (range 21-94) and 51 were male. Compared with final diagnosis the MCM5 assay had a sensitivity for malignancy of 65.4% compared with 25.0% for cytology. In the 72 patients with paired MCM5 assay and biliary brush cytology, MCM5 demonstrated an improved sensitivity (55.6% vs 25.0%; P=0.0002) for the detection of malignancy.
  
  
  
  Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology.
authors.affiliation: Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London NW3 2PF, UK.
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Keane
authors.affiliation: Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London NW3 2PF, UK.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Huggett
authors.affiliation: Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BG, UK.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Chapman
authors.affiliation: Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BG, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Johnson
authors.affiliation: Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BG, UK.
authors.forename: George J
authors.initials: GJ
authors.lastname: Webster
authors.affiliation: Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London NW3 2PF, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, Gower St, London WC1E 6BT, UK.
authors.forename: James
authors.initials: J
authors.lastname: Mackay
authors.affiliation: Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London NW3 2PF, UK.|Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BG, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000378:metabolism; D003581:Cytodiagnosis / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008871:Microvilli / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C489423:MCM5 protein, human