Abstract 895: Glycopeptides in pancreatic adenocarcinoma
Authors: Remmers Neeley A. , Anderson Judy M. , Singh Pankaj K. , Hollingsworth Michael A. 
Published: June 2012

There were an estimated 43,140 new cases and 36,800 deaths due to pancreatic adenocarcinoma (PA) for 2010, ranking PA as the third leading cause of cancer related death. Virtually all long term survivors are diagnosed early but these survivors only account for 7% of those diagnosed 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; Neu5Acα2-3Galβ1-3[Fucα1-4]GlcNAc) that can be present as an O-linked oligosaccharide on glycoproteins and is expressed at relatively low levels on normal epithelial cells. Unfortunately, approximately 15% of the population cannot synthesize SLeA due to a lack of expression of the necessary enzyme to add the final fucose residue thus lowering the sensitivity of the assay. We investigated the expression of other O-linked glycans expessed in PA – sialyl Tn (STn; NeuAcα2-6GalNAc), Tn (GalNAc), T (Galβ1-3GalNAc) and sialyl LewisC (SLeC; Neu5Acα2-3Galβ1-3GlcNAc) – and the aberrant expression of mucin core proteins. In an effort to establish an antigenic signature for PA, we have performed immunohistochemical analysis on primary tumor and liver metastatic tumor samples from 28 autopsy patients diagnosed with PA to analyze their mucin and glycosylation expression. STn and Tn were expressed in the majority of patients in both the primary and liver metastatic tumors and SLeC expression mirrored that of SLeA albeit at lower levels. In those patients lacking SLeA expression SLeC could be detected indicating that the CA19-9 test could be enhanced when combined with these glycans. MUC1, MUC4 and MUC6 were detected in ≫70% of the primary tumor samples analyzed. We also investigated the potential of mucin glycopeptides (STn/Tn on MUC1, STn/Tn on MUC4, and ST/T on MUC1) in providing a unique signature for PA. We found that both STn/Tn on MUC1 and STn/Tn on MUC4 were expressed in &gt;90% of the primary tumor samples analyzed while ST/T on MUC1 was predominantly expressed in normal controls. Differences were also observed in the mucin and glycan signatures between primary and liver metastatic tumors. For example, MUC2 and MUC5B were expressed in the liver metastases while MUC17 was restricted to primary tumor. Finally, we analyzed the expression of MUC1, MUC4, STn/Tn on MUC1, STn/Tn on MUC4, STn and Tn in 4 pancreatitis samples. These antigens were observed in 75-100% of these cases indicating that these particular antigens may by induced by the early inflammatory process leading towards a pro-tumorigenic microenvironment. We conclude that glycopeptide structures comprise an expression pattern unique to PA with potential as biomarkers of early disease and warrant further investigation. Supported by grants U01CA111294 and U01CA128437 from the NCI

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 895. doi:10.1158/1538-7445.AM2011-895