No abstract

When compared to prior reports, this study suggests a lower frequency of MSI among the Puerto Rican population. The higher prevalence of MLH1 mutations correlates with previous studies of protein expression among the Hispanic community including Colombian, Uruguay and Brazilian populations.

Pancreatic cancer (PaCa) is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect PaCa at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic PaCa precursors that comprise nearly 50% of pancreatic cysts detected incidentally via cross-sectional imaging. Since IPMNs can progress from low- and moderate-grade dysplasia to high-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish a living biobank of patient-derived organoids (PDO) from IPMNs. IPMN tumors and adjacent normal pancreatic tissues were successfully harvested from 15 patients with IPMNs undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between May of 2017 and March of 2019. Organoid cultures were also generated from cryopreserved tissues. Organoid count and size were determined over time by both Image-Pro Premier 3D Version 9.1 digital platform and Matlab application of a Circular Hough Transform algorithm, and histologic and genomic characterization of a subset of the organoids was performed using immunohistochemistry and targeted sequencing, respectively. The success rates for organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different epithelial subtypes showed different morphologies in vitro, and organoids recapitulated histologic and genomic characteristics of the parental IPMN tumor. In summary, this pre-clinical model has the potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for early detection and targets for chemoprevention.

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect pancreatic cancer at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic pancreatic cancer precursors that comprise nearly 50% of pancreatic cysts detected incidentally via computed tomography (CT) scans. Since IPMNs can progress from low- and moderate-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish the first living biobank of IPMN tumor organoids. IPMN tumors and adjacent normal pancreatic tissues were harvested from 15 patients undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between 2017 and 2019. Following immunohistopathologic analysis of primary tissues, organoid cultures were generated, expanded, and cryopreserved. Furthermore, organoid cultures were generated from cryopreserved tissues as well. Count and size of the organoids over time was determined via the Image-Pro Premier 3D Version digital platform. Genomic characterization of the organoids was performed through DNA fingerprinting, and a subset of cases were sequenced. The success rates of organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different IPMN subtypes tissues showed different morphologies in vitro, with the low- and moderate-grade pancreatobiliary subtypes showing the highest proliferation rates. This model has potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for detection and targets for chemoprevention. Citation Format: Dayana Reverón, Francisca Beato, Gina DeNicola, Antonio Ortiz, Barbara Centeno, Kun Jiang, Daniel Jeong, Mokenge Malafa, Pamela Hodul, Kaleena Deszi, Jennifer Permuth, Jason Fleming. Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C46.