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 (Po0.01 and P ¼ 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 ¼ 0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; Po0.001 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.

Whole genome RNA expression profiling of endoscopic biliary brushings provides data suitable for biomarker discovery in cholangiocarcinoma

“…Intensity of staining was reported by a histopathologist using a widely used semi quantitative scoring system (0; no staining, +; weak, ++; moderate and +++; strongly positive staining) [18]. The number of biliary epithelial cells stained positive were also scored (0; <5%, +; 5%–20%, ++; 20%–50% and +++; >50% stained positive [12]. Comparison of results was performed for both number of cells positively stained and intensity of staining.…”

“…A potential confounding factor in biliary samples is leukocyte RNA contamination as a result of biliary infection, particularly in those with biliary obstruction. Previous work has shown that RNA from bile and/or biliary brushings can be useful for qPCR when measuring small numbers of highly expressed genes [12–13]. …”

Serum and bile biomarkers for cholangiocarcinoma

“…Therefore, sandwich ELISA of serum MUC5AC seems to be promising and provides clinical value for diagnosis and prognosis of CCA. MUC4 and MUC5AC were also investigated by Matull et al [19 ] using real-time reverse transcriptase-PCR (qPCR) and Western blot in serum and bile samples prospectively collected from 72 patients with biliary obstruction of different causes, including 39 CCA and seven PSC. Serum MUC5AC protein was detected in 17 out of 39 (44%) CCA but not in the other malignancies.…”

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment

“…26,28 The gel-forming mucin MUC5ac is a marker for biliary tract cancer. 29 Findings show that MUC 3, 4, and 5ac are overexpressed in ampullary malignancies and that MUC3 is an independent predictor of poor survival. 30 The expression of mucins differs between tumors with pancreaticobiliary and intestinal differentiation.…”