ECP 2023 Abstracts

S127 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 up-regulation of the examined pro-inflammatory and pro-fibrotic mol- ecules in cultured human EC. Transient overexpression of SET7 deter- mined significant increases in E-selectin, ICAM-1, VCAM-1, Col IV, FN and LM transcript levels in EC. Conclusion: Dysregulated epigenetic mechanisms have been increas- ingly implicated in pathoetiology of diabetes-associated vascular complications. Histone methyltransferase SET7 induces H3K4me1 modification, an epigenetic histone imprint that is associated with a long-lasting transcriptional activation and responsiveness of the target genes. In this study we provide evidence that pharmacological inhibi- tion of SET7 limits the pro-inflammatory and pro-fibrotic responses in diabetic kidney. The data suggest that pharmacological targeting of SET7 could be considered for further pre-/clinical assessment as potential supportive therapeutic strategy in DKD. This work was supported in part by grants from the Ministry of Research, Innovation and Digitization, CNCS – UEFISCDI (PN- III-P1-1.1-TE-2021-0180, PN-III-P4-ID-PCE-2020-1898), within PNCDI III and from the Romanian Academy. PS-23 | Poster Session Digestive Diseases Pathology - Liver/ Pancreas PS-23-001 Metal mining of liver tissues using Laser Ablation-Inductively Coupled PlasmaMass Spectrometry provides multi-elemental resolutive spatial distribution P. Allaume*, J. Le Maitre, B. Turlin, E. Bardou-Jacquet, O. Loreal, M. Ropert-Bouchet *Rennes University Hospital, Departement of Pathology, France Background & objectives: Metal homeostasis disorders contribute to liver disease. Knowledge of metal distribution abnormalities may improve disease understanding. Our objective is to perform metal imaging in paraffin embedded human liver biopsies by using Laser Ablation coupled with Inductively Coupled Mass Spectrometry (LA-ICP-MS). Methods: Liver biopsy samples were collected in the University Hospi- tal, Rennes from patients exhibiting either a cirrhosis, a genetic hemo- chromatosis (GH) or a Wilson’s disease (WD). Standard histological stains assured a morphological control. LA-ICP-MS was performed on 3μm thick unstained paraffin slides with a high spatial resolution (10μm spot size). Elemental distribution of 56Fe, 65Cu, 66Zn, 78Se and 24Mg was analysed. Results: LA-ICP-MS analysis of 20 paraffin embedded human liver biopsy samples (5 cirrhosis, 10 GH, 5 WD) enables easy recognition of histological structures including portal tracts, fibrous septa, cen- trolobular veins and iron-free foci in GH. Iron and copper distribu- tion correlates with the morphological analysis using standard stains (Perl’s and rhodanine respectively). Morever, LA-ICP-MS is able to accurately demonstrate local iron and copper distribution in advanced cirrhosis patients, whereas dry weight biochemical quantification may result in misquantification. LA-ICP-MS also enables investigation of the distribution of metals inaccessible to standard histological analy- sis (66Zn, 78Se and 24Mg). Results are consistent with the known literature. Conclusion: LA-ICP-MS is an innovative, highly sensitive and resolutive method for simultaneous multi-metal imaging in paraffin embedded human liver samples. The obtained data can be superposed with standard histological procedures. Pre-analytic constraints are few, enabling an easy integration into care workflow. Biochemical determination, current gold standard for liver trace element quantifi- cation, does not enable topographical analysis. LA-ICP-MS is there- fore a powerful technique that open new opportunities for studying metal homeostasis disorders, and a potential tool in the practice of pathology. PS-23-002 Evaluation of tumour budding, desmoplastic reaction, and lym- phocytic infiltration in predicting survival for pancreatic ductal adenocarcinoma A. Alpsoy*, K. Şimşek, A. Yavuz, B. Altunay, M. Karaca, B. Ünal, C.I. Bassorgun, A.M. Tatli, G.Ö. Elpek *Akdeniz University Department of Pathology, Turkey Background& objectives: Recently morphological assessment of tumour budding(TB) has been revealed as a promising prognostic finding to pre- dict tumour behaviour in Pancreatic Ductal Adenocarcinoma(PDAC). Therefore, this study aims to investigate the prognostic role of TB, des- moplastic reaction(DR), and lymphocytic infiltration in PDAC. Methods: The study group consisted of 100 patients with PDAC (from 2005 to 2020). Both peritumoral and intratumoral budding was assessed according to the ITBCC. Desmoplastic reaction (DR) was classified into three groups based on the maturation of tumour stroma. The evaluation of TIL was determined semi-quantitatively based on a 5% cutoff value. Statistical analysis was performed using SPSS version 27. Results: A strong relationship was observed between the intratu- moral and peritumoral budding scores (r:0,890). An inverse correla- tion existed between a high peritumoral budding score and a low TİL (p<0,001). The peritumoral budding score and TİL were associated with T, lymphovascular invasion, lymph node metastasis, and stage (p<0,005). Univariate analysis indicated poor survival rates were associated with lymphovascular invasion, lymph node metastasis, high peritumoral, and intratumoral budding (p<0.001). On multivariate Cox regression analysis, intratumoral and peritumoral budding scores were determined as independent prognostic factors. Conclusion: Our findings support that the evaluation of TB according to ITBCC criteria can be performed to stratify patients with PDAC for treatment and prognosis. In addition, the close relationship between intratumoral and peritumoral budding warrants further research with larger series to determine whether intratumoral budding assessed in small biopsies provides to determine the behaviour and the treatment strategy for unresectable PDAC. PS-23-003 Assessment of PD-L1 expression correlated with the MSI status in extrahepatic cholangiocarcinoma R. Ardeleanu*, S. Zurac, T. Voiosu, C.I. Diaconu, M. Birligea, D. Raduta, A. Cernat-Stefan, M. Matanie, C. Popp *Colentina Clinical Hospital, Romania Background & objectives: We aim to predict the prognostic and therapeutic value of the Programmed-death Ligand 1 (PD-L1) marker expression in extrahepatic cholangiocarcinomas, along with a potential correspondence with the microsatellite instability (MSI) status, as a prospect of targeted immunotherapy in these patients. Methods: This retrospective study included 34 patients who underwent tissue sampling from radiologically proven infiltrative tumours, with a histological diagnosis ranging from atypical biliary epithelium to carcinoma. We performed immunohistochemical stains for the four mismatch repair proteins (MSH2, MSH6, MLH1, PMS2) and evaluated the PD-L1 membranous expression in both atypical and tumour cells, with a positive cutoff point set at 5%. Results: Five cancer biopsies out of 30 (16,6%) showed PD-L1 positiv- ity, with the highest percentage of expression being 10% and a male sex predominance (80%) within this group. Surprisingly, two of these patients displayed positive staining in biopsy samples of atypical biliary epithelium as well. Four cases demonstrated a microsatellite instability status: two from the PD-L1 positive category, one being a carcinoma with negative labelling for all the four markers and one with MSH6 and MLH1 loss in the abnormal biliary specimen. The remainder of two were PD-L1 negative, comprising a PMS2 and MLH1