Mucins in human neoplasms: Clinical pathology, gene expression and diagnostic application

Abstract

Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. Our immunohistochemical studies demonstrated that MUC1 or MUC4 expression is related to the aggressive behavior and poor outcome of human neoplasms. MUC2 is expressed in indolent pancreatobiliary neoplasms, but these tumors sometimes show invasive growth with MUC1 expression in invasive areas. MUC5AC shows de novo high expression in many types of precancerous lesions of pancreatobiliary cancers and is an effective marker for early detection of the neoplasms. The combination of MUC1, MUC2, MUC4 and MUC5AC expression may be useful for early detection and evaluation of the potential for malignancy of pancreatobiliary neoplasms. Regarding the mechanism of mucin expression, we have recently reported that expression of the mucin genes is regulated epigenetically in cancer cell lines, using quantitative MassARRAY analysis, methylation-specific polymerase chain reaction analysis and chromatin immunoprecipitation analysis, with confirmation by the treatment with 5-aza-2'-deoxycytidine and trichostatin A. We have also developed a monoclonal antibody against the MUC1 cytoplasmic tail domain, which has many biological roles. Based on all of the above findings, we suggest that translational research into mucin gene expression mechanisms, including epigenetics, may provide new tools for early and accurate detection of human neoplasms.

Predictive biomarkers and effectiveness of MUC1-targeted dendritic-cell-based vaccine in patients with refractory non-small cell lung cancer

“…We consider that patient selection, namely selection of patients with high expression of target antigen on cancer cells, is critical for tumor-antigen-targeted cancer immunotherapies, and that MUC1-targeted vaccines are not effective against NSCLC with limited or no expression of MUC1. MUC1 is reported as highly expressed on adenocarcinoma cells [Yonezawa et al 2011]; however, our MUC1 immunohistochemistry data demonstrate that the expression of MUC1 on more than 60% of adenocarcinoma cells occurs in only 40.3% of patients (data not shown). Accordingly, to avoid an ineffective anticancer therapy, we examined MUC1 expression on NSCLC cells by immunohistochemistry, and only patients with MUC1 expressed by more than 60% of cancer cells were eligible.…”

“…The tumor antigen MUC1 has been reported to be abundantly expressed in many types of cancers, such as breast, lung and colon cancers [Lakshmanan et al 2015;Yonezawa et al 2011], and is strongly immunogenic [Quinlin et al 2007;Wright et al 2000;Kohlgraf et al 2004;Kontani et al 2001]. The tandem repeat domain in the core protein of MUC1 contains antigenic epitopes that are recognized by T cells in a major histocompatibility complex (MHC)-independent manner [Barnd et al 1989;Wright et al 2008].…”

Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein status as well as expression of epithelial-to-mesenchymal transition markers and cell cycle regulators at the stage of liver metastasis

“…Two clusters were distinguished: a cluster of a small number of samples with low MUC1/MUC1core expression, and a large cluster of cases with higher MUC1/MUC1core expression (specific data not shown). This addressed the issue of glycosylation patterns in neoplastic tissues, which was recently examined and reviewed [46,[73][74][75]. MUC1 over-expression was previously recognized as a unfavorable prognostic factor in PDAC [73,76].…”

Histopathologic and Immunohistochemical Characterization of Human Gastric Oxyntic Mucosa with Parietal Cell Protrusions and Investigation into the Association Between Such Mucosal Changes of the Stomach and Use of Proton Pump Inhibitors

“…In addition, we examined immunohistochemically and evaluated quantitatively expression of markers of proper gastric epithelial cell differentiation as follows: MUC5AC in foveolar cells 18) , AQP4 in parietal cells and chief cells 19) , H+/K+-ATPase in parietal cells 20) , MUC6 in mucous neck cells 18) , and MIST1 in chief cells 21) . We also assessed cells for Ki-67 positivity 22) .…”