Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology

Br J Cancer. 2017 Jan;116(3):349-355. doi: 10.1038/bjc.2016.447. Epub 2017 Jan 12.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology.

Publication types

  • Clinical Trial
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Ducts / metabolism
  • Bile Ducts / pathology*
  • Bile Ducts / ultrastructure
  • Cell Cycle Proteins / analysis*
  • Cell Cycle Proteins / metabolism
  • Cytodiagnosis / methods*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Male
  • Microvilli / metabolism
  • Microvilli / pathology*
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Young Adult

Substances

  • Cell Cycle Proteins
  • MCM5 protein, human