Abstract 2720: Glycosylation of Mucins Expressed in Pancreatic Adenocarcinoma

Abstract

Abstract Glycosylation of mucins expressed by pancreatic adenocarcinoma There were an estimated 42,470 new cases and 35,240 deaths due to pancreatic adenocarcinoma (PA) for 2009, ranking PA as the third leading cause of cancer related death. Virtually all long term survivors are diagnosed early but only 7% are detected in the early stages of disease thus highlighting the need for an early diagnostic test. CA19-9, the only current clinical serum-based assay used to monitor PA, detects an oligosaccharide blood group antigen Sialyl Lewisa (sLeA) with the structure (Neu5Acα2-3Galβ1-3[Fucα1-4]GlcNAc), which can be present on glycolipids or as an O-linked oligosaccharide on glycoproteins, and is expressed at relatively low levels on the surfaces of normal epithelial cells. The full spectrum of proteins on which the CA19-9 epitope is expressed has never been defined. CA19-9 is differentially expressed on mucins, which are extensively glycosylated. The CA19-9 test lacks high specificity for PA, as CA19-9 is commonly elevated in patients with benign chronic pancreatitis and other malignant diseases. Different epithelial tissues and cell types produce distinct combinations of mucin-type core proteins, and the expression patterns of these are generally altered during different disease processes including malignant transformation. Mucin expression is deregulated in cancer, which results in aberrant expression and glycosylation of mucin core proteins. We employed immunohistochemistry and immunofluorescence to show the unique mucin and glycosylation patterns seen in tissue specimens from patients diagnosed with PA. Deglycosylation of samples immunoprecipitated from cancer cell lines and pancreatic cancer patient tissue specimens was used to enable detection of mucin core proteins. Immunoaffinity chromatography was used to isolate CA19-9 from patient ascites and serum samples and mass spectrometry was used to analyze the core proteins. Results show that pancreatic cancers expressing the mucin core proteins MUC1, MUC4 and MUC5AC carry the CA19-9 epitope. Preliminary results suggest that a strategy to detect the CA19-9 tumor antigen and its cognate mucin core protein(s) will improve the performance characteristics of this assay. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2720.