ECP 2023 Abstracts

S130 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Methods: A total of 48 cases of pancreatic cancer which were surgically resected with (NAT group, n=24) or without NAT (UFS group, n=24) in Seoul National Bundang Hospital were included. Tissue microar- ray (TMA) was constructed followed by spatial transcriptomic analysis using NanoString GeoMx Digital Spatial Profiler Transcriptomic Atlas. IHC for CD3, CD20, CD4, CD8, CD68, CD163 were also performed. Results: When comparing pan-CK-positive cells in NAT and UFS group, FGD6 and CPB1 gene showed increased expression in NAT group, while SUMO4 and FOXN2 gene expression was increased in UFS group (all q<0.1). In CD45-positive cells and remainder cells, PPP1R10 and MFAP4 expression was increased in CAP score 3 group compared with CAP score 2 group (all q<0.1). IHC analysis revealed higher CD3, CD4, CD8, CD68, and CD163-positive cells in CAP score 2 group compared with CAP score 3 group (all p<0.05). Higher CD68- positive cell density was associated with shorter overall survival (OS) (p=0.020) while higher CD8-positive cell density was marginally asso- ciated with prolonged progression-free survival (PFS) (p=0.050). Conclusion: FGD6 which is known to be related with micropinocytosis, can be considered as possible target in NAT group. Increased PPP1R10 and MFAP4 expression, and a paucity of immune cells could be pre- dictive markers of response to the NAT. In addition, CD8- and CD68- positive cell density can be prognostic indicator of pancreatic cancer. PS-23-011 Multi-regional analysis of combined hepatocellular-cholangiocar- cinoma reveals histologic diversity and molecular clonality Y.E. Kim*, H.Y. Na, H. Kim, J.H. Kim, S. Ahn *Department of Pathology, Seegene medical centre, Seoul, Korea, Republic of Korea Background & objectives: Combined hepatocellular-cholangiocarci- noma (cHCC-CC) is a rare liver tumour that exhibits both hepatocytic and biliary differentiation within the same tumour. The histology and genomic alteration of recurrent/metastatic cHCC-CC are poorly understood. Methods: We selected six cHCC-CCs of which recurrent or meta- static tumours were histologically confirmed, consisting of four classic cHCC-CCs and two intermediate cell carcinomas. Clinico- pathologic features including histology of primary, and recurrent/ metastatic tumours were evaluated. Next generation sequencing was performed in 16 multi-regional and longitudinal tumour samples. Results: Among four classic cHCC-CC patients, three cHCC-CCs had a previous history of HCC, and two of them were developed after transarterial chemoembolization. In a total of 13 samples from four cHCC-CC patients, the most frequent pathologic variants were TP53 (46.2%), TERT promoter (38.5%), ARID1A mutations (23.1%), and MET amplification (30.8%). Large proportion of mutations were shared by each HCC and CC component, suggesting monoclonal origin of this entity. In ICs, ATM mutation was detected in one patient, and genes commonly altered in HCCs or CCs were not detected. Recurrent or metastatic lesions presented more mutations than primary lesions. Conclusion: The histology of recurrent/metastatic tumour of cHCC- CC was variable. The genomic profiling of cHCC-CCs revealed similar genomic alterations to HCC, and suggested a monoclonal origin of each HCC and CC component. Genetic alterations in ICs were different from either HCC or CC, suggesting the distinct nature of this tumour. PS-23-013 An immunohistochemical study of MAGE proteins in hepatocel- lular carcinoma M. Lambropoulou*, S. Tologkos, V. Papadatou, A. Panagiotopoulos, T. Alexiadis, A. Mitrakas, C. Alexiadi, V. Lampropoulou, C. Nikolaidou, G. Tripsianis *Histology-Embryology Lab., Medical Department, Democritus Uni- versity of Thrace, Alexadroupolis, Greece Background & objectives: The MAGE protein family consists of more than forty members that have been found overexpressed in vari- ous malignancies. This study was designed to detect MAGE-C1 and MAGE-C2 expression in hepatocellular carcinoma, and to correlate their expression with clinicohistopathological parameters. Methods: We used 57 samples from patients with hepatocellular car- cinoma. MAGE-C1 and MAGE-C2 expression was evaluated using immunohistochemistry via monoclonal antibodies for both proteins. Statistical data analysis was performed using the SPSS, version 19.0 (IBM). The chi-squared test and multivariate logistic regression were used to assess the association of individual MAGE-C1 and MAGE-C2 expression with patients’ clinicopathological parameters. Results: Higher expression of MAGE-C1 and C2 was found in males (p<0.001, p<0.001), patients with history of HBV/HCV (p=0.008, p<0.001), higher grade tumours (p<0.001, p<0.001), patients with multiple nodules (p<0.001, p<0.001), patients with higher AFP lev- els (p<0.001, p<0.001) and was also correlated with higher chance of death (p=0,008, p=0.008). When multiple logistic regression was performed age, presence of HBV/HCV, higher grade, more nodules, higher AFP and status remained independent prognostic factors for high MAGE-C1 expression, while all the parameters tested except for age were independent prognostic factors for high MAGE-C2 expression. Conclusion: Our research is in accordance with limited studies in the literature which have shown that MAGE proteins could be used as prognostic markers in a variety of malignancies. Based on our results MAGE-C1 and MAGE-C2 are potential biomarkers for prognosis and a perspective therapeutic target in hepatocellular carcinoma. How- ever due to the limited literature on the subject and the small samples amount of our study further research would be appropriate. PS-23-014 GAD2 is a highly specific marker for neuroendocrine neoplasms of the pancreas M. Lennartz*, N.B. Dünnebier, N. Blessin, D. Hoeflmayer, S. Dwert- mann Rico, S. Kind, C. Fraune, N. Gorbokon, C. Hube-Magg, F. Büscheck, A. Menz, G. Sauter, R. Simon, S. Minner, C. Bernreuther *University Medical Center Hamburg-Eppendorf, Germany Background & objectives: Glutamate decarboxylase 2 (GAD2) is the most important inhibitory neurotransmitter and plays a role in insulin- producing β-cells of pancreatic islets. The limitation of GAD2 expres- sion to normal brain and pancreatic islet cells makes GAD2 a potential immunohistochemical diagnostic marker. Methods: To evaluate the diagnostic utility of GAD2 immunohistochem- istry (IHC), a tissue microarray containing 19,202 samples from 152 dif- ferent tumour entities and 608 samples of 76 different normal tissue types was analysed. Data on progesterone receptor (PR) expression were avail- able on 15,232 tumours from a previous study. Results: GAD2 positivity occurred in 20 of 152 tumour categories including 5 tumour categories with at least one strongly positive case. GAD2 positivity was most frequent in neuroendocrine carcinomas (58.3%) and neuroendocrine tumours (63.2%) of the pancreas, followed by granular cell tumours (37.0%) and neuroendocrine tumours of the lung (11.1%). GAD2 in <10% of cases occurred in 16 other tumour entities including paraganglioma, medullary thyroid carcinoma, and small cell carcinoma of the urinary bladder. In a cohort of 95 pancre- atic and 380 extra-pancreatic neuroendocrine neoplasms, GAD2 had a sensitivity of 64.2% and a specificity 96.3% for pancreatic tumour origin while PR had a sensitivity of 56.8% and a specificity of 92.6%. Conclusion: GAD2 IHC is a highly useful diagnostic tool for the iden- tification of pancreatic origin in case of neuroendocrine neoplasms with unknown site of origin. The particular strength of GAD2 is its high speci- ficity for pancreatic origin. For the distinction of a pancreatic tumour