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Clinical Trial
. 2017 Jan;116(3):349-355.
doi: 10.1038/bjc.2016.447. Epub 2017 Jan 12.

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

Margaret G Keane  1 , Matthew T Huggett  1 , Michael H Chapman  2 , Gavin J Johnson  2 , George J Webster  2 , Douglas Thorburn  1 , James Mackay  3 , Stephen P Pereira  1   2
Affiliations
Clinical Trial

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

Margaret G Keane et al. Br J Cancer. 2017 Jan.

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.

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Conflict of interest statement

JM is a clinical advisor to Varleigh DX (UK) Ltd. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Stages of development of the MCM5 immunocolorimetric ELISA assay.
Figure 2
Figure 2
ROC curve for patients with paired biliary brush cytology and MCM5 assay.
Figure 3
Figure 3
Comparison of sensitivity, specificity, NPV and PPV in patients with paired cytology and MCM5 biliary brush assay.
See this image and copyright information in PMC

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