Diagnosis of Pancreaticobiliary Malignancy by Detection of Minichromosome Maintenance Protein 5 in Biliary Brush Cytology

Overview

Journal Br J Cancer

Specialty Oncology

Date 2017 Jan 13

PMID 28081547

Citations 8

Authors

Margaret G Keane

Matthew T Huggett

Michael H Chapman

Gavin J Johnson

George J Webster

Douglas Thorburn

James Mackay

Stephen P Pereira

Affiliations

Soon will be listed here.

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.

Citing Articles

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Ney A, Garcia-Sampedro A, Goodchild G, Acedo P, Fusai G, Pereira S Front Oncol. 2021; 11:699401.

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Genome-wide investigation of the clinical significance and prospective molecular mechanism of minichromosome maintenance protein family genes in patients with Lung Adenocarcinoma.

Liu K, Kang M, Liao X, Wang R PLoS One. 2019; 14(7):e0219467.

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MCM5 promotes tumour proliferation and correlates with the progression and prognosis of renal cell carcinoma.

Gong B, Ma M, Yang X, Xie W, Luo Y, Sun T Int Urol Nephrol. 2019; 51(9):1517-1526.

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References

Loddo M, Kingsbury S, Rashid M, Proctor I, Holt C, Young J . Cell-cycle-phase progression analysis identifies unique phenotypes of major prognostic and predictive significance in breast cancer. Br J Cancer. 2009; 100(6):959-70. PMC: 2661794. DOI: 10.1038/sj.bjc.6604924. View

Gress T . Molecular diagnosis of pancreatobiliary malignancies in brush cytologies of biliary strictures. Gut. 2004; 53(12):1727-9. PMC: 1774308. DOI: 10.1136/gut.2004.046177. View

Keane M, Marlow N, Pereira S . Novel endoscopic approaches in the diagnosis and management of biliary strictures. F1000Prime Rep. 2013; 5:38. PMC: 3768325. DOI: 10.12703/P5-38. View

Freeman A, Morris L, Mills A, Stoeber K, Laskey R, Williams G . Minichromosome maintenance proteins as biological markers of dysplasia and malignancy. Clin Cancer Res. 1999; 5(8):2121-32. View

Stoeber K, Swinn R, Prevost A, Halsall I, Dilworth S, Marr J . Diagnosis of genito-urinary tract cancer by detection of minichromosome maintenance 5 protein in urine sediments. J Natl Cancer Inst. 2002; 94(14):1071-9. DOI: 10.1093/jnci/94.14.1071. View

Lee J . [Multidetector-row CT of malignant biliary obstruction]. Korean J Gastroenterol. 2006; 48(4):247-55. View

Harewood G, Baron T, Stadheim L, Kipp B, Sebo T, Salomao D . Prospective, blinded assessment of factors influencing the accuracy of biliary cytology interpretation. Am J Gastroenterol. 2004; 99(8):1464-9. DOI: 10.1111/j.1572-0241.2004.30845.x. View

Blow J, Hodgson B . Replication licensing--defining the proliferative state?. Trends Cell Biol. 2002; 12(2):72-8. PMC: 3604914. DOI: 10.1016/s0962-8924(01)02203-6. View

Lazaridis K, Gores G . Cholangiocarcinoma. Gastroenterology. 2005; 128(6):1655-67. DOI: 10.1053/j.gastro.2005.03.040. View

10.

Burnett A, Bailey J, Oliver J, Ahlawat S, Chokshi R . Sensitivity of alternative testing for pancreaticobiliary cancer: a 10-y review of the literature. J Surg Res. 2014; 190(2):535-47. DOI: 10.1016/j.jss.2014.04.014. View

11.

Williams G, Stoeber K . Cell cycle markers in clinical oncology. Curr Opin Cell Biol. 2007; 19(6):672-9. DOI: 10.1016/j.ceb.2007.10.005. View

12.

Luna L, Kipp B, Halling K, Sebo T, Kremers W, Roberts L . Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology. 2006; 131(4):1064-72. PMC: 1769444. DOI: 10.1053/j.gastro.2006.08.021. View

13.

Anderson M, Appalaneni V, Ben-Menachem T, Decker G, Early D, Evans J . The role of endoscopy in the evaluation and treatment of patients with biliary neoplasia. Gastrointest Endosc. 2012; 77(2):167-74. DOI: 10.1016/j.gie.2012.09.029. View

14.

Williams G, Swinn R, Prevost A, De Clive-Lowe P, Halsall I, Going J . Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates. Br J Cancer. 2004; 91(4):714-9. PMC: 2364793. DOI: 10.1038/sj.bjc.6602028. View

15.

Kalaitzakis E, Levy M, Kamisawa T, Johnson G, Baron T, Topazian M . Endoscopic retrograde cholangiography does not reliably distinguish IgG4-associated cholangitis from primary sclerosing cholangitis or cholangiocarcinoma. Clin Gastroenterol Hepatol. 2011; 9(9):800-803.e2. PMC: 3246637. DOI: 10.1016/j.cgh.2011.05.019. View

16.

Wharton S, Chan K, ANDERSON J, Stoeber K, Williams G . Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis. Neuropathol Appl Neurobiol. 2001; 27(4):305-13. DOI: 10.1046/j.0305-1846.2001.00333.x. View

17.

Hamer O, Feuerbach S . How useful is integrated PET and CT for the management of pancreatic cancer?. Nat Clin Pract Gastroenterol Hepatol. 2006; 3(2):74-5. DOI: 10.1038/ncpgasthep0407. View

18.

Kalaitzakis E, Webster G, Oppong K, Kallis Y, Vlavianos P, Huggett M . Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones. Eur J Gastroenterol Hepatol. 2012; 24(6):656-64. DOI: 10.1097/MEG.0b013e3283526fa1. View

19.

Williams G, Stoeber K . Clinical applications of a novel mammalian cell-free DNA replication system. Br J Cancer. 1999; 80 Suppl 1:20-4. View

20.

De Bellis M, Sherman S, Fogel E, Cramer H, Chappo J, McHenry Jr L . Tissue sampling at ERCP in suspected malignant biliary strictures (Part 1). Gastrointest Endosc. 2002; 56(4):552-61. DOI: 10.1067/mge.2002.128132. View