Abstract 3075: EUS-guided biopsy of pancreatic mass lesions for the development of patient-derived organoids in Puerto Rico

Abstract

Abstract Pancreatic cancer is an aggressive cancer that is diagnosed early in only 10% of cases and has a 5-year survival rate of less than 9%. The process in determining the optimal treatment for each patient is both long and tedious - and current strategies do not enable therapy optimization at the individual level. The incidence rate for pancreatic cancer in Puerto Rico between 2013 and 2017 was 8.2%, which is lower than the rate reported for non-Hispanic whites and blacks (16% and 12.9%, respectively). The causes for such health disparity are unknown but it is very likely associated with changes at the genomic and tissue microenvironment level at the sub-population level. To identify pathological markers in a more patient-specific manner, patient-derived models need to be integrated into studies of drug screening and efficacy. Patient-derived organoids (PDO) are becoming a potential model for diagnosis and the study of disease progression due to their ability to recreate the pathology of the tumor in the patients. Although several PDO studies have highlighted their potential for therapeutic applications, the ability to successfully culture and propagate these using standard methods has not been shown in samples collected from the Hispanic population. We assessed the feasibility of establishing PDOs from tissue specimens of a pancreatic mass lesion from Puerto Rican patients using standard methods for pancreatic organoids. A total of 9 samples were collected from endoscopic ultrasound fine-needle biopsies to examine the pathological features of the sample and the retention of the parental tumor characteristics in culture. All tissue specimens were cultured in Matrigel domes within 24 hours of extraction and organoid establishment was monitored for 7-8 days. All samples were positive for pancreatic adenocarcinoma but only around 50% of them were successfully cultured in Matrigel. High ATP levels were observed in tumor organoids after one week in culture which is indicative of a high cell viability. Examination of pathological markers indicated that all samples were negative for epidermal growth factor (EGFR), 5/6 were positive for smooth muscle actin (SMA), 4/6 were positive for Vimentin, and 1/6 were positive for CA 19.9. Absence of EGFR was unexpected as this marker is highly expressed and abundant in 40-70% of pancreatic cancers. Samples with high levels of SMA, a fibroblast marker, resulted in a higher organoid yield than samples with no SMA present. Overall, the data suggests that the presence of fibroblasts is supportive of organoid establishment in culture and that standard culture methods need to be optimized to increase organoid yields. Future work will seek to increase the sample size to test alternative propagation methods and examine drug sensitivity in patient-derived pancreas organoids of the Puerto Rican population. Citation Format: Andrea S. Flores Perez, Janet Mendez Vega, Ana M. Reyes Ramos, Carlos Micames, Madeline Torres Lugo, Maribella Domenech. EUS-guided biopsy of pancreatic mass lesions for the development of patient-derived organoids in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3075.