title: MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer.
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.
authors.affiliation: The Institute of Hepatology, Division of Medicine, Royal Free & University College London Medical School, London, UK.
authors.forename: W R
authors.initials: WR
authors.lastname: Matull
authors.forename: F
authors.initials: F
authors.lastname: Andreola
authors.forename: A
authors.initials: A
authors.lastname: Loh
authors.forename: Z
authors.initials: Z
authors.lastname: Adiguzel
authors.forename: M
authors.initials: M
authors.lastname: Deheragoda
authors.forename: U
authors.initials: U
authors.lastname: Qureshi
authors.forename: S K
authors.initials: SK
authors.lastname: Batra
authors.forename: D M
authors.initials: DM
authors.lastname: Swallow
authors.forename: S P
authors.initials: SP
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000378:metabolism*; D001661:Biliary Tract Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D055264:Mucin-4; D009077:Mucins / Q000097:blood* / Q000378:metabolism*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C524658:MUC4 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055264:Mucin-4; D009077:Mucins