Molecular Characterization and Xenotransplantation of Pancreatic Cancer Using Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA)

Simple Summary Existing treatments for pancreatic cancer have limited effectiveness due to the genetic diversity between pancreatic tumors from different patients. By propagating the original tumor into a mouse (creating a xenograft) it may be possible to study each individual tumor further and plan personalized therapy. EUS-FNA is a technique which has recently become a routine method for obtaining a biopsy from a patient without the need for surgery. In this study, we tested whether EUS-FNA can also be used to obtain tumor tissue of sufficient volume and purity to establish a corresponding xenograft and to perform a genetic analysis. We found that in the majority of cases, both mouse xenografts and genetic analyses can be performed successfully. Xenograft tumors were found to maintain the characteristics and genetic expression from the original patient tumors and to be vulnerable to infection by a virus used to destroy cancer cells.Abstract Pancreatic cancer has one of the worst prognoses among all malignancies and few available treatment options. Patient-derived xenografts can be used to develop personalized therapy for pancreatic cancer. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) may provide a powerful alternative to surgery for obtaining sufficient tissue for the establishment of patient-derived xenografts. In this study, EUS-FNA samples were obtained for 30 patients referred to the Ottawa Hospital, Ottawa, Ontario, Canada. These samples were used for xenotransplantation in NOD-SCID mice and for genetic analyses. The gene expression of pancreatic-cancer-relevant genes in xenograft tumors was examined by immunohistochemistry. Targeted sequencing of both the patient-derived tumors and xenograft tumors was performed. The xenografts' susceptibility to oncolytic virus infection was studied by infecting xenograft-derived cells with VSV triangle 51-GFP. The xenograft take rate was found to be 75.9% for passage 1 and 100% for passage 2. Eighty percent of patient tumor samples were successfully sequenced to a high depth for 42 cancer genes. Xenograft histological characteristics and marker expression were maintained between passages. All tested xenograft samples were susceptible to oncoviral infection. We found that EUS-FNA is an accessible, minimally invasive technique that can be used to acquire adequate pancreatic cancer tissue for the generation of patient-derived xenografts and for genetic sequencing.