More than 2% of the adult population of the US harbors a pancreatic cyst and the increasing use of abdominal imaging is likely to increase the diagnosis of these lesions as incidental findings. Because these cysts can either be self-limiting lesions or represent true precursors to deadly invasive adenocarcinomas, they pose a difficult clinical management problem. There are three main forms of pancreatic cystic neoplasms, serous cystic adenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). SCAs are thought to be totally benign whereas IPMNs and MCNs are often associated with an invasive component. The ultimate goal of this proposal is to develop clinically useful biomarkers that can distinguish these cyst types and alter clinical decision-making. This goal is practical now due to previous successes of this SPORE in the areas of genomic analysis, biomarker development and pancreatic cyst analysis. To achieve this goal, we propose a detailed molecular-analysis of neoplastic cells from all three main types of pancreatic cyst neoplasms (Aim #1). These molecular findings will be used to develop cyst fluid biomarkers (Aim #2). Cyst fluid was chosen as the target clinical sample because of promising preliminary results and because cyst fluid is routinely available in the clinic at critical decision points. The best biomarkers developed in Aim #2 will be correlated with clinical findings and outcomes in both a retrospective (Aim #3) and prospective (Aim #4) manner. The above studies will identify molecular changes that underlie the pathogenesis of pancreatic cyst development and should allow the development of clinically useful cyst fluid biomarkers.

Public Health Relevance

Pancreatic cysts are relatively common and certain types can be precursors to deadly adenocarcinoma of the pancreas. Because of the risk of morbidity and death associated with either the under or over treatment of pancreatic cysts, better diagnostic methods for distinguishing pancreatic cyst type would be highly useful. The goal of this proposal is to develop molecular markers to improve the diagnosis of pancreatic cyst.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Johns Hopkins University
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Llosa, Nicolas J; Cruise, Michael; Tam, Ada et al. (2015) The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 5:43-51
Eshleman, James R; Norris, Alexis L; Sadakari, Yoshihiko et al. (2015) KRAS and guanine nucleotide-binding protein mutations in pancreatic juice collected from the duodenum of patients at high risk for neoplasia undergoing endoscopic ultrasound. Clin Gastroenterol Hepatol 13:963-9.e4
Zhen, David B; Rabe, Kari G; Gallinger, Steven et al. (2015) BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genet Med 17:569-77
Patel, Kalpesh; Iacobuzio-Donahue, Christine A; Gormley, Paul E et al. (2015) Are we systematically under-dosing patients with fluorouracil? J Clin Oncol 33:e36-7
De Remigis, Alessandra; de Gruijl, Tanja D; Uram, Jennifer N et al. (2015) Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival. Int J Cancer 136:127-37
Sutcliffe, Catherine G; Schultz, Kathleen; Brannock, Julitta M et al. (2015) Do people know whether they are overweight? Concordance of self-reported, interviewer-observed, and measured body size. Cancer Causes Control 26:91-8
Black, Chelsea M; Armstrong, Todd D; Jaffee, Elizabeth M (2014) Apoptosis-regulated low-avidity cancer-specific CD8(+) T cells can be rescued to eliminate HER2/neu-expressing tumors by costimulatory agonists in tolerized mice. Cancer Immunol Res 2:307-19
Kojima, Masatsugu; Murata, Satoshi; Mekata, Eiji et al. (2014) Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine. J Immunother 37:147-54
Wu, Xinyan; Renuse, Santosh; Sahasrabuddhe, Nandini A et al. (2014) Activation of diverse signalling pathways by oncogenic PIK3CA mutations. Nat Commun 5:4961
Amato, Eliana; Molin, Marco Dal; Mafficini, Andrea et al. (2014) Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol 233:217-27

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