Abstract B91: Primary tumor xenograft establishment from pancreatic resection specimens.

Abstract

Background: As part of Canada9s International Cancer Genome Consortium (ICGC) pancreatic cancer genome sequencing project and to develop a large number of patient-derived cancer models for functional studies, we initiated a program to systematically establish primary xenografts from patients who underwent pancreatic cancer resection. Methods: Informed consent was obtained from patients scheduled for resection of their pancreatic tumors. Tumor samples were harvested from the resected specimens and placed into transport medium within 30 minutes after the pancreatectomies. Samples were implanted into the subcutaneous and orthotopic (pancreatic) sites of nonobese diabetic (NOD) SCID mice. Tumor growths were recorded weekly and animals were sacrificed when the tumors reached 1.5 cm3 humane endpoint. Tumor fragments were processed for reimplantation into new hosts, serially for up to five generations, as well as for histopathology evaluation, cryopreservation, and snap-frozen tissue banking. Results: Between September 2008 and December 2011, primary tumors from 110 consented pancreatic cancer patients were obtained and implanted. The pathology reported pancreatic ductal adenocarcinoma in 91 of these patients. Xenograft tumors formed in 65 of 91 (71%) ductal cancers. Among 26 samples that failed to engraft, 2 were characterized as carcinoma in situ, and four samples were found to contain no tumor cells. The engraftment rate reached 76% (65/85) when tumor cells were present in the implanted samples. Xenograft tumor growth rates were highly variable with majority of the tumors reaching endpoint within 3 months after the implantation. Histological features were highly similar between xenograft tumors and their corresponding patient primary tumors. Conclusions: A great majority of invasive adenocarcinomas from pancreatic resection can form primary tumor xenografts in NOD SCID mice. Appropriate pathological sampling of the primary tumor is one of the crucial elements for the high success rate. Citation Format: Emin Ibrahimov, Nhu-An Pham, Fannong Meng, Mayleen Sukhram, Dianne Chadwick, Stefano Serra, Patricia Shaw, Corwyn Rowsell, Calvin Law, John McPherson, Steven Gallinger, Ming- Sound Tsao. Primary tumor xenograft establishment from pancreatic resection specimens. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B91.