ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 positivity for neuroendocrine markers, SATB2 and had a prolif- erative index Ki67 between 40 and 50%. They both expressed Polyomavirus on immunohistochemistry. Final diagnosis was Merkel cell carcinoma. Intestinal tumour was positive for neu- roendocrine markers and TTF1. Ki67 labelled 80% of the cells. Final diagnosis was metastasis of large cell neuroendocrine car- cinoma of lung. Chest tomography was secondarily performed and confirmed this diagnosis. Conclusion: NEC of the digestive system are rare tumours with multiple morphological mimics. The pathologist must always favour the diagnosis of a secondary localization and push the investigations before making the diagnosis of primary NEC of the digestive system. PS-14-010 Different patterns of prostate specific membranous antigen expression in tumour-associated neovasculatur among neu- roendocrine neoplasms of GI-tract - an immunohistochemical study targeted on its theranostic use V. Wild*, K. Mielert, S. Roth, A. Rosenwald, R. Werner, A. Mein- ing, A. Weich *Institute of Pathology, University of Würzburg, Germany Background & objectives: Tumour vascularization as a therapeutic target is gaining importance in an increasing number of solid tumours. In this context, the expression of prostate specific membranous antigen (PSMA) in intratumoral vessels has led to increased interest with regard to PSMA-directed therapy. Methods: We examined PSMA expression on tumour-associated vessels in specimens of different neuroendocrine neoplasms of the digestive system (n=16 NET-G1, n=16 NET-G2, n=8 NET-G3 and n=14 NEC) by immunohistochemistry. If positively stained vessels were present, their number was counted in hotspot regions and related to the area. Results: PSMA expression in intratumoral vessels was detected in 2/16 NET-G1 (12,5%), 3/16 NET-G2 (18,7%), 5/8 NET-G3 (62,5%) and 7/14 NEC (50%). We found differences in the distribution (intratumoral versus marginal or in the area of the invasion front) as well as in the number and density of stained vessels. Conclusion: Comparable to other solid tumour entities, in neuroen- docrine neoplasms PSMA expression in intratumoral, tumour-derived vessels is associated with higher tumour-grade and aggressiveness. As PSMA-directed therapy in metastatic prostate cancer is an already well-established theranostic concept, opportunities are now also emerg- ing in the context of vascular PSMA expression of solid tumours. This could open up the possibility of PSMA-directed diagnostic work-up and therapy in aggressive neuroendocrine neoplasms whose therapeutic options have been limited so far. PS-15 | Poster Session Molecular Pathology PS-15-001 Digimir test: a novel pipeline for mir-371a-3p quantification using droplet digital PCR in liquid biopsies of testicular germ cell tumour patients J. Lobo*, J.P. Sequeira, V. Constâncio, T. Brito-Rocha, C. Car- valho-Maia, I. Braga, J. Maurício, R. Henrique, C. Jerónimo *IPO Porto, Portugal Background& objectives: miR-371a-3p is the most reliable liquid-biopsy biomarker for diagnosis and monitoring of testicular germ cell tumour (TGCT) patients. Current studies have focused on RT-qPCRmethodologies, but some challenges remain (pre-amplification and normalization). Droplet digital PCR (ddPCR) may overcome these challenges. Methods: In this work, we provide a report of a ddPCR-based pipeline for quantification of miR-371a-3p (the DigiMir pipeline) and compare it with two common RT-qPCR protocols. A total of 107 plasma samples were investigated in the validation setting. All requirements for validation of ddPCR pipelines were followed, including appropriate controls, spike-in, temperature gradient and limits of blank, detection and quantification. Results: The DigiMir pipeline showed a good performance in the intra-operator, inter-operator, inter-synthesis and inter-extraction tests. It detected TGCTs in a manner representative of tumour burden, with a sensitivity and specificity of 94% and 100%, respectively, outperforming the combined sensitivity of all three classical serum tumour markers available currently in routine (61.5%). All non-TGCT testicular masses were negative, as was a patient with hepatocarcinoma showing high serum levels of AFP, further assuring the specificity of the test. One patient with constitutive slight elevation of AFP (generating clinical challenges) was negative for the miR-371a-3p and remained disease-free under surveillance. The single patient showing disease progression maintained high miR-371a-3p levels at follow-up. Conclusion: Therefore, in this proof-of-concept investigation, we have showed that the DigiMir pipeline constitutes a new promising methodology for accurately reporting miR-371a-3p in the clinical setting. ddPCR is a suitable methodology for quantifying microRNAs in liquid biopsy samples of patients with the accuracy needed for precision medicine. Funding: The authors would like to acknowledge the support of the Programa Operacional Competitividade e Internacionalização (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the project EpiMarkGermCell (PTDC/MEC-URO/ 29043/2017). The authors would also like to acknowledge the support of MSD (“Prémio de Investigação em Saúde”), Banco Carregosa / Secção Regional do Norte da Ordem dos Médicos (SRNOM) and Fundação Rui Osório de Castro / Millennium bcp. JL is recipient of a fellowship from FCT - Fundação para a Ciência e Tecnologia—(SFRH/ BD/132751/2017). VC received the support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/DR20/11790013. PS-15-002 Differential gene expression of nystagmus-associated genes in chronic traumatic encephalopathy, Parkinson`s disease, and Alzheimer`s disease F.V. De Los Reyes* *Department of Neuromuscular Research, National Center of Neu- rology and Psychiatry, Philippines Background & objectives: The research aimed to determine whether the genes that presented with nystagmus as part of their clinical pres- entation were differentially expressed in the brains of patients with Parkinson’s Disease (PD), Chronic Traumatic Encephalopathy (CTE), and Alzheimer’s Disease (AD). Methods: The data was derived from the available NCBI SRA datasets that allowed public domain use. The database search yielded 10 PD patients, 13 AD patients, 10 CTE patients, and 6 CTE with AD patients. The RNA sequence from the brain samples of the patients underwent differential expression analysis using the web-based platform Galaxy and R version 4.1.0 with R Studio. Results: Identifying the nystagmus-associated genes among the genes that were expressed in the brain samples of patients with PD, AD, CTE, and CTE with AD showed that there were only 21 genes out of the 28,395 retrieved genes in the mRNA sequence of the S140