ECP 2023 Abstracts

S304 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Results: Histopathological examination in the CNS of mice infected with Eptesicus furinalis (EPBRV), Myotis nigricans (MNBRV) and positive control (CVS-31) were characterized by non-suppurative meningoencephalomyelitis with lymphocytic perivascular cuffing, neuronal necrosis, neuronophagia, neuropil vacuolation, presence of microglial nodules and Purkinje cells depopulation, which could be associated with higher levels of cell death-related molecules. The production of TNF-α, iNOS and Caspase-3 by neurons and astrocytes were significantly (p<0.05) higher in EPBRV than in MNBRV and positive control, mainly in the hippocampus and cortex. Conclusion: Greater expression of molecules correlated with cell death in EPBRV-infected mice may trigger the extension of neuronal damage and be related to the various symptoms observed in the infec- tion, such as tremors and paralysis. Our results also provide important insights into understanding the biological characteristics and interac- tion of RABV isolated from insectivorous bats with the host. They may help advance new therapies, epidemiological surveillance, and the implementation of a better rabies control strategy, particularly in developing countries. Funding: This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP –Process No. 2017/08215-7) and Instituto Pasteur/São Paulo/Brazil (Process No. IP02/17). E-PS-15 | E-Posters Molecular Pathology E-PS-15-001 Unravelling the sarcoma puzzle: insights from next generation sequencing on diagnosis and treatment in 100 cases B.K. Aktas*, P. Bulutay, I. Kulac, C. Aydin Mericoz *Koç University, School of Medicine, Department of Pathology, Turkey Background & objectives: The molecular characterization of sarco- mas has become essential for accurate diagnosis and treatment. This study highlights the advantages and limitations of RNA-based next generation sequencing (NGS) in over 100 sarcoma cases, emphasizing its diagnostic and therapeutic impact. Methods: We reviewed the Koç University Department of Pathol- ogy Laboratory Information System for all sarcoma cases sequenced between 2019 and 2023, including 100 consecutive cases (128 stud- ies) using four commercial targeted panels: ArcherDx Sarcoma Panel, ArcherDx CTL Panel, ArcherDx FusionPlex Solid Tumour Panel, and ArcherDx VariantPlex Solid Tumour Panel, in respective numbers and percentages (72%, 31%, 16%, 5%). Results: Reliable sequencing studies were conducted for 90 (90%) cases, while 10 (10%) failed quality tests. Pathogenic alterations were identified in 61 (61%) cases. The most common alterations were EWSR1 fusions, with FLI1 being the most frequent partner. NGS results significantly altered the initial diagnosis in 19 cases (19%) and confirmed it in 24 (24%) cases. Notably, NGS clarified diagnoses for eight cases initially diagnosed as malignant small round cell tumours: five had EWSR1-FLI1 fusion (Ewing sarcoma), and three had CIC-DUX4 fusion (CIC-rearranged sarcoma). We also identified targetable alterations such as NTRK fusion (n=2) and KIT mutation (n=3). Conclusion: Targeted NGS panels prove to be reliable and informa- tive, enabling pathologists to confirm and refine diagnoses while serving as valuable prognostic and predictive tools. Importantly, NGS-guided diagnosis changes led to treatment modifications, emphasizing the need for integrating molecular test results with morphological and clinical findings to ensure accurate diagnosis and treatment planning. E-PS-15-002 Increase in expression of exosomal long non-coding RNA H19 in the blood of patients with castration-resistant prostate cancer is associated with the development of docetaxel resistance I. Bakhtogarimov*, E. Pudova, A. Kobelyatskaya, I. Katunina, M. Fedorova, A. Snezhkina, G. Krasnov, A. Kudruavtseva *EIMB RAS, Russia Background & objectives: Profiling of circulating lncRNA is a promising direction for the new predictive markers search. The aim of the study is to identify lncRNAs potentially associated with disease progression in the dynamics of treatment of patients with castration- resistant prostate cancer (CRPC). Methods: The study included 11 patients with CRPC treated with docetaxel, from which libraries were prepared and RNA-Seq was performed on the Illumina platform. Differential expression analysis was performed between docetaxel response and onset of progression samples using the edgeR package in the R statistical environment. Sta- tistical analysis of results between time periods for each patient was performed in paired mode. Results: According to the bioinformatic analysis results of the obtained RNA-Seq data, a statistically significant increase in differential expres- sion of H19 was detected in the group with the beginning of progres- sion of CRPC on the background of docetaxel therapy by 5.93 times (LogFC = 2.57; p-value QLF test = 0.002). Spearman rank correlation analysis also showed a statistically significant correlation between H19 expression and the period of progression onset in patients (rs = 0.43; p-value = 0.04). Conclusion: Thus, based on the study, it was shown that an increased level of H19 expression is statistically significantly associated with the development of resistance to docetaxel and can be considered as a potential predictive marker in CRPC. This research was financially supported by the Russian Science Foun- dation, grant 22-24-01093. E-PS-15-003 MET immunohistochemistry reflex testing in non-small cell lung carcinoma. A real world prospective study in a single centre (LPCE, Nice, France) C. Bontoux*, V. Hofman, M. Abboute, S. Goffinet, E. Long-Mira, S. Lassalle, M. Ilié, P. Hofman *Laboratory of Clinical and Experimental Pathology, Hospital-Inte- grated Biobank (BB- 0033-00025), Pasteur Hospital, IRCAN Team 4, Inserm U1081, CNRS 7284, FHU OncoAge, Université Côte d’Azur, Nice, France Background & objectives: Development of new MET inhibitors have recently shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC) in clinical trials, in particular in NSCLC with MET overexpression. However, MET IHC reflex testing is not currently recommended in international guidelines. Methods: We evaluated prospectively MET expression (SP44 clone) as a reflex testing in 429 NSCLC consecutively diagnosed in biopsies, cytological or surgical samples between January 2022 and January 2023. MET+ was defined by an H-score greater than or equal to 150 of tumour membrane staining and MET high as tumour having strong (3+) staining of ≥50% tumour cells. Results: Whatever sample types the MET H-score and the MET inten- sity was significantly correlated with the histological subtype, being superior in adenocarcinoma than in squamous cell carcinoma. MET H-score ≥150 was observed in 55% of surgical specimens, in 38% of biopsy and in 32% samples. 48% of all samples showed a MET high expression.