Wahb Ata
Research Mentor: Marina Pasca Di Magliano
Mentor Department: Surgery/ Cell & Developmental Biology, Medicine
Author(s): Wahb Ata, Jude Okoye, Marina Pasca Di Magliano
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 29
Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly form of cancer, due to the fact it is being diagnosed in its most advanced stages. PDAC development has been characterized to develop from precursor lesions such as pancreatic intraepithelial neoplasia (PanIN) and in a stepwise progression. PanINs are small ductal shaped epithelial neoplasms that can be defined by levels of dysplasia (low-grade to high-grade). Although the understanding of PDAC heterogeneity is well documented, there is little knowledge of the heterogeneity of the human PanIN lesions and cancer risk molecular signatures. Methods: In collaboration with the Gift of Life program at Michigan, we have so far received 115 donor pancreata from individuals from the age of 21 to 76 years. To identify the PanIN lesions standard histology was used. To validate the presence of the genes at the protein level, multiplex immunofluorescent staining was performed on the tissue sections. KRT17 and GATA6 expression was analyzed quantitatively by Fiji (ImageJ). Regions of interest were segmented, and fluorescence intensify thresholds were applied to classify cells into negative, low, and high expression categories, this allowed for assessment of abundance across tumor and donor specimens. Results: Histological analysis indicated that most of the donor pancreata were confined with low-grade PanIN lesions, while one sample displayed a high-grade PanIN. Significant heterogeneity among PanIN lesions was observed through quantitative image-based analysis of KRT17 and GATA6 expression. A subset of PanINs exhibited basal-like epithelial features such as KRT17, and some displayed the classical epithelial features such as GATA6. The mean fluorescent intensity (MFI) of KRT17 was much lower within the donor PanINs compared to the tumor epithelial cells (p < 0.05), while no significant difference was seen in GATA6 expression (p > 0.05). Tumor samples exhibited higher relative abundance of KRT17? epithelial cells compared to donor PanIN lesions, highlighting phenotypic heterogeneity across disease states. Conclusion: Overall, this study revealed evidence that PanIN lesions are not uniform but are heterogenous at the microscopic and molecular level. They may illustrate similar features to PDAC early on in disease development. This highlights the importance of assessing PanIN lesions as a means of identifying individuals at risk of developing pancreatic cancer.
