Glypican-1 and glycoprotein 2 bearing extracellular vesicles do not discern pancreatic cancer from benign pancreatic diseases

// Fabrice Lucien 1, * , Vivian Lac 2, * , Daniel D. Billadeau 3 , Ayelet Borgida 4 , Steven Gallinger 5 , Hon S. Leong 1, 2 1 Department of Urology, Mayo Clinic, Rochester, MN, USA 2 Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada 3 Department of Oncology, Mayo Clinic, Rochester, MN, USA 4 Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada 5 Department of Surgery, University Health Network, Toronto, ON, Canada * These authors have contributed equally to this work Correspondence to: Hon S. Leong, email: leong.hon@mayo.edu Keywords: pancreatic cancer; flow cytometry; extracellular vesicles; glypican-1; liquid biopsy Received: December 04, 2018 Accepted: January 09, 2019 Published: February 01, 2019 ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that is clinically asymptomatic in its early stages of development. Non-invasive testing for pancreatic cancer biomarkers would significantly improve early detection and patient care. Extracellular vesicles (EVs) are circulating tumor fragments present in the blood and may express cancer specific biomarkers that would enable early detection of pancreatic cancer. We tested the utility of a blood test enumerating EVs positive for the pancreas-specific marker Glycoprotein 2 (GP2) and the putative pancreatic cancer marker Glypican-1 (GPC1) in patients with PDAC. Various levels of GPC1-positive and GP2/GPC1-positive EVs were detected in PDAC patients but were not significantly higher than benign pancreatic disease (BPD) patients. The sensitivity and specificity of the GPC1 EV test was 26.67% and 87.50% respectively, whereas the sensitivity and specificity for the GPC1+GP2 EV test was 23.33% and 90.00% respectively. Immunohistochemistry of GPC1 expression in a tissue microarray of PDAC and various controls also did not demonstrate specificity of GPC1 to PDAC. Hence, enumeration of GPC1-positive EVs, solely or in conjunction with GP2, was unable to effectively distinguish between BPD and pancreatic cancer.