ECP 2023 Abstracts

S312 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Methods: Twenty-four rectal NETs that were endoscopically resected were enrolled. To evaluate the miRNA expression profile relevant to common genetic mutations in rectal NETs, we used next-generation sequencing and the NanoString nCounter miRNA Expression assay. KEGG pathway analysis predicted the possible target signalling path- way correlated with dysregulated miRNAs. Results: 19 rectal NETs (79.2%) showed more than 1 mutation in the 24 cancer-related genes (TP53 [29.2%], FBXW7 [20.8%], CDKN2A [16.7%], PTEN [16.7%]). 7 miRNAs (hsa-miR-769-5p, hsa-miR- 221-3p, hsa-miR-34a-5p, hsa-miR-181c-5p, hsa-miR-1246, hsa- miR-324-5p, hsa-miR-361-3p) were down-regulated in the tumours harbouring FBWX7 mutation (p<0.0001). Hierarchical clustering of miRNA expression profiles separated the tumour group with a high mitotic index from the mutated group. Among these down-regulated miRNAs, using the KEGG pathway, hsa-miR-769-5p was correlated with extracellular matrix-receptor interaction and lysine degradation (FDR<0.05). Among clinicopathological factors, the up-regulated hsa- miR-3934-5p was linked with increased mitotic count (FDR<0.05). No changes in miRNAs expressions involved in tumour size >1 cm, lymphovascular invasion, and Ki-67 index could be identified. Conclusion: In conclusion, using miRNA expression profiling, we have identified different miRNA signatures involved in either FBXW7 mutation or high mitotic index in rectal NETs, which may play an essential role in tumour behaviours. Funding: the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2022R1F1A1065335) E-PS-15-030 Evaluation of the expression of 148A and 192 mirRNA associa- tion with postoperative complications in patients undergoing liver transplant at Fundación Santa Fe de Bogotá R.D.P. Lopez-Panqueva*, D.M. Grajales Urrego, P.C. Trujillo Morales, H.A. Gonzalez, R.E. Andrade Perez, M.L. Tapias, A. Vera Torres *Fundación Santa Fe de Bogotá, Department of Pathology and Labora- tory Medicine, Universidad de Los Andes, Bogotá, Colombia Background & objectives: Post-transplant complications include acute rejection and recurrence of the underlying disease. MicroRNAs are proposed as specific and sensitive biomarkers for early detection of liver damage. Our objective was to evaluate the association between miRNAs expression and the occurrence of complications. Methods: The expression of miRNAs 148a and 192 was evaluated in relation to the appearance of complications in 38 patients undergo- ing liver transplantation, through a nested case-control study. Serum plasma samples were taken from the patients before and after the trans- plant, RNA extraction and rt-qPCR were subsequently performed, clin- ical history data were collected, and retrospective statistical analysis was performed. Results: The appearance of complications such as acute cellular rejec- tion and recurrence of post-transplant hepatic steatosis was associated with overexpression of miRNAs 148a and 192 in blood (p <0.0001). Gender was a statistically significant variable, since men had fewer post-transplant complications than women (p=0.004).History of smoking, obesity and blood group did not have a statistically signifi- cant relationship with respect to the risk of post-transplant complica- tions. History of non-alcoholic hepatic steatosis (p=0.002), diagnosis of hepatocellular carcinoma as a complication of hepatic steatosis (p=0.0032), and a high MELD score (p=0.023); were associated with an increase in miRNAs 148a and 192, as well as post-transplant complications. Conclusion: Circulating miRNAs have emerged as promising highly specific and sensitive diagnostic and prognostic biomarkers for the non- invasive detection of diseases, due to their capacity for gene regulation at the post-transcriptional level, in different pathologies. Our study was able to show that they are sensitive predictors of complications after liver transplantation; so in the future they could be more reliable mark- ers to predict the risk of complications in these patients. E-PS-15-031 Mechanisms of resistance to EGFR tyrosine kinase inhibitor ther- apy in lung adenocarcinomas M. Mihálffy*, E. Tóth, L. Báthory-Fülöp *National Institute of Oncology, Hungary Background & objectives: EGFR mutations in non-small cell lung carcinomas (NSCLCs) represent potential targets for treatment using tyrosine kinase inhibitors. Our aim was to identify and analyse the various types of resistance mechanisms (including the most common T790M) that influence the therapeutic response. Methods: We screened plasma (circulating tumour DNA) and tho- racic fluid samples, cytology smears, cell blocks, biopsy and resection specimens from patients with lung adenocarcinoma who received first or second-generation TKI treatment. For the T790M mutation we used EGFR monogenic testing (COBAS EGFR and EGFR AmoyDx kit). For diagnosing other types of resistance, we employed multigenic NGS (IonTorrent S5, Oncomine Focus Assay). Results: We detected the T790M mutation in approximately 50% of cases where we could identify the original EGFR mutation, but the detection rate depended on the type of sample used. The rest of cases showed a variety of different changes, including individual EGFR, KRAS, CDK4, FGFR, MET, HER2 amplification, PIK3CA mutation, MET 14 exon skipping or a group with the presence of several concur- rent genomic alterations as well. So some of the identified resistance mechanisms were eligible for different targeted therapy. We also dis- tinguished a case where histological transformation into squamous cell carcinoma phenotype took place. Conclusion: NSCLCs with mutated EGFR account for approximately 12% (11% in our cohort) of all lung cancers in Europe. While treatment with TKIs is often effective, the emergence of resistance mechanisms poses a therapeutic challenge. The identification of the commonly occurring T790M mutation or any other targetable resistance mecha- nism is of paramount importance, since the information aids the selec- tion of the most appropriate therapy for the patient. Nevertheless, the simultaneous presence of other resistance mechanisms or non-T790M resistance requires further investigation. E-PS-15-032 Novel NTRK2 gene rearrangement in CNS neoplasia: pitfall or new finding? D. Morotti*, E. Antelmi, A.C. Bettini, E. Costi, G. Ghirardi, M. Ias- cone, S. Intagliata, C. Lucca, R. Merli, M. Motta, R. Muni, G. Pezzetti, E. Rigoli, M. Sicignano, A. Gianatti *Department of Pathology, Papa Giovanni XXIII Hospital, Bergamo, Italy Background & objectives: Neurotrophic tyrosine receptor kinase (NTRK 1/2/3) gene fusions are rare but present across multiple tumour types and their frequencies can vary by cancer type. Testing is essential to identify patients who may benefit from target therapy. Methods: Two high grade glioma patients were tested with a DNA- based NGS custom panel detecting NTRKs gene rearrangements. Pan-TRK IHC and a FISH test with a break- apart probe for NTRK2 gene were performed. Moreover, we ran a PCR with designed primers followed by Sanger sequencing and, finally, the IdyllaTM GeneFusion Assay was applied to test the chimeric transcript. Results: A novel gene fusion PHLPP1(5’)-NTRK2(3’) was found in two cases by NGS DNA sequencing with allelic frequencies of 15,4% and 30,4% respectively. QC parameters and coverage were suitable.