1. ¹The Institute of Hepatology, Division of Medicine, Royal Free & University College London Medical School, London, UK
2. ²Galton Laboratory, Department of Biology, University College London, London, UK
3. ³Department of Histopathology, University College London Hospitals NHS Foundation Trust, London, UK
4. ⁴Oncology Department, Cancer Research UK Targeting and Imaging Group, Royal Free University College London Medical School, London, UK
5. ⁵Eppley Cancer Institute, Department of Biochemistry and Molecular Biology, University of Nebraska, Omaha, NE, USA
6. ⁶Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK

Correspondence: Dr SP Pereira, The Institute of Hepatology, Royal Free & University College Medical School, 69-75 Chenies Mews, London WC1E 6HX, UK. E-mail: stephen.pereira@ucl.ac.uk

⁷These authors contributed equally to this work.

Received 8 February 2008; Revised 27 March 2008; Accepted 28 March 2008; Published online 13 May 2008.

Abstract

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.