Abstract B024: Exploring the temporal dynamics of pancreatic cancer through post-mortem tumor analysis: A pilot case study

Abstract

Abstract Introduction Pancreatic cancer is a lethal disease with an incidence little higher than the mortality rate. Great advances in oncology have been made in recent years with new treatment strategies for many cancers, leading to substantial improvement in patient outcome. The prognosis for pancreatic cancer patients, however, remains dismal and chemotherapy is still standard of care. An increased understanding of the temporal evolution and resistance mechanisms of pancreatic cancer during chemotherapy is necessary to improve patient outcome. To this end, the Chemotherapy, Host response And Molecular dynamics in Periampullary cancer study (CHAMP) was initiated in 2018. It is an ongoing, prospective observational trial in which blood samples are taken from patients at each chemotherapy cycle. Recently, the CHAMP- Extended Tissue Analysis (ETA) study was initiated, wherein selected patients enrolled in the CHAMP-study undergo targeted autopsies. The aim of this study was to compare the expression of selected immunohistochemical (IHC) markers and the quality of DNA in tumor tissue from an ante-mortem resected metastasis to the ileum and post-mortem collected tumor tissue in the first patient enrolled in the CHAMP-ETA study. Methods The autopsy was performed by a senior pathologist in accordance with standard procedure guidelines and all visible tumor was collected for analysis. The post-mortem interval (PMI) was 44 hours. Multiple tissue cores from formalin-fixed paraffin-embedded tumor tissue from the surgical resection and different tumor sites from the autopsy were assembled into a single tissue microarray (TMA) block. DNA was extracted from adjacent tissue cores obtained in parallel with the TMA-construction, and the quality examined by qPCR. IHC staining of standard diagnostic markers CK7, CK20, CDX2 and the proliferation marker Ki67 was performed on the TMA. Results In line with the expected, both normal and tumor tissue in the pancreas displayed a higher degree of autolysis compared to the metastases. Tumor areas surrounded by a more dense stroma tended to be less autolytic. CK20 and CDX2 expression was negative in all samples, both ante-mortem and post-mortem. CK7 was highly expressed in all tumor samples with an ever-stronger intensity in the post-mortem samples. Of note, CK7 was also strongly expressed in the tumor stroma of the post-mortem samples, but not in the pre-mortem samples. Ki67 expression was significantly higher in ante-mortem than in post-mortem samples. The extracted DNA was of sufficient quality in all tested post-mortem samples. Conclusion The results demonstrate that the DNA quality is sufficient after a PMI of 44 hours. The conditions for IHC staining are less optimal but may be sufficient for some markers. Access to post-treatment tumor tissue is an important complement to on-treatment biomarker studies, and of vital importance to understand the molecular events leading to terminal disease. Citation Format: Sofie Olsson Hau, Jasmine Webster, Alexandra Petersson, Jakob Eberhard, David Gisselsson, Karin Jirström. Exploring the temporal dynamics of pancreatic cancer through post-mortem tumor analysis: A pilot case study [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B024.