ECP 2023 Abstracts

S313 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Pan-TRK immunohistochemistry was positive in both cases but inef- fective in ruling out ectopics from endogenous gene expression. FISH test analyses were negative for NTRK2 breakage, while PCR results confirmed the presence of a rearrangement. Sanger sequencing con- firmed the breakpoint on the NTRK2 gene but not the PHLPP1 one due to the high homology of the analysed trait with other genomic regions. RT-PCR of mRNA analyses revealed a consistent expression imbalance between 3’ and 5’ of NTRK2 gene. Conclusion: Pan-TRK antibody is a good screening tool to detect NTRKs gene rearrangements in many tumours but not in the CNS, being TRK receptors usually expressed in nervous tissues. A DNA- NGS custom panel based on hybrid capture enrichment is efficient to detect rearrangements but new gene involvement needs an addi- tional workload. RNA analysis by real-time PCR confirmed the loss of NTRK2 transcript amount caused by translocation. A RNA-NGS panel based on targeted RNA enrichment could identify actively transcribed new chimeric fusions. E-PS-15-033 Placenta molecular characteristics in intrauterine feotal demise E. Nardi*, I. Seidita, I. Abati, C. Donati, F. Castiglione, C. Serena, F. Mecacci, F. Petraglia *Section of Anatomic Pathology, Department of Health Sciences, Uni- versity of Florence, Italy Background & objectives: Placenta may have a central role for explaining foetal death as intrauterine foetal demise (IUFD) has been correlated with an impaired secretion of some placental factors. The aim of this study was to investigate molecular mechanism involved in idiopathic IUFD. Methods: Ten cases of singleton pregnancy ended in IUFD were selected, excluding pregnancies complicated by foetal anomalies and diseases that might affect placentation. Ten placentas collected from healthy singleton term pregnancies served as controls. Histopathological examination of the selected samples was made, and RNA was extracted. The quantification of mRNA expression levels was performed using real-time polymerase chain reaction. Results: No significant difference in maternal and foetal sex distribu- tion between the two groups whereas gestational age and birth weight were significantly lower in the cases compared to the group control. The histological examination of the placentas ended in IUFD can be classified in vascular malperfusion or placental dysfunction. The control placentas did not show any pathological changes. Using real-time PCR, difference in placental mRNA expression of dif- ferent proteins were observed: IL-6 (P= 0.0495) and VEGFR2 (P= 0.0305) resulted more expressed in samples of IUFD compared to con- trol, while activin A (P= 0.0098), ABCB1 (P= 0.0450) and ABCG2 (P= 0.0232) expression was lower in IUFD. Conclusion: The present study showed that placenta from pregnancies with IUFD have an increase in inflammatory factors (IL-6 and S1P) as well as a decrease in the expression of growth factors (activin A) and molecules implicated in trophoblast migration and invasion. This could explain an inflammatory state and growth defect underlying the process that leads to IUFD. E-PS-15-034 Molecular analysis of non-small cell lung carcinomas in the National Institute of Oncology, Hungary K. Nemeth*, E. Tóth, L. Báthory-Fülöp *National Institute of Oncology, Hungary Background & objectives: In the treatment of non-small cell lung carcinomas several new targeted agents have become available in recent years, and the benefits of targeted therapy have led to the need for detailed molecular pathology testing in lung adenocarcinomas. Methods: We performed Oncomine™ focus assay on Ion-Torrent S5 (NGS) platform.The classification of detected variants and the therapeutic relevance of pathogenic variants was evaluated using Ion Reporter™. In cases not suitable for sequencing, COBAS tests were used. Parallel ALK (Ventana ALK D5F3 CDx Assay), ROS1 (Cell Signaling D4D6) and PD-L1 immunohistochemistry (DAKO 22C3 PharmDx kit) were also performed. Results: 1412 adenocarcinoma and 474 squamous cell carcinoma samples included 1049 biopsies, 367 cytological samples and 470 surgical resection specimens were investigated. 37% of adenocarcinoma cases were suitable for sequencing. Histo- logical features, specimens’ types and molecular results were ana- lysed. 554 cases (39%) of adenocarcinomas showed KRAS muta- tions. 160 of 1412 tumours (11%) were EGFR mutant. We found ALK and ROS1 fusion in 21 and 5 cases. Regarding PD-L1 expression, Tumour Proportion Score (TPS) were negative in 26,2%, 48,5% showed 1-49% TPS and 25,3% were more than or equal to 50% of the 423 squamous cell carcinoma. The distribu- tion was nearly equal in the 1088 adenocarcinoma cases, 33,4%, 35,1% and 31,5%, respectively. Conclusion: In our laboratory, KRAS mutation was more common compared to the literature’s data, and we found fewer ALK and ROS1 fusions which is probably associated with higher incidence of smok- ing in Hungary. A significant proportion of small biopsy and cytol- ogy samples were suitable for sequencing. PD-L1 positivity (TPS>1%) was higher among squamous cell carcino- mas compared to adenocarcinomas. Our results show a good correla- tion with the literature, which is an important indicator of the quality of the lab’s work. E-PS-15-035 A combined digital and molecular approach to precision oncology: the lung and breast cancer use cases F. Pagni*, D. Seminati, G. Cazzaniga, V.L. L’Imperio *University Milan Bicocca Department of Medicine and Surgery, Italy Background & objectives: The use of molecular tests has grown rap- idly in recent years as they have been shown to provide more accu- rate and detailed information about the genetic characteristics of the tumour, leading to more effective treatment options. Methods: In order to assess the impact of molecular testing on a pathology department, data for BC and NSCLC was extracted from the LIS over the year period from 2020 to 2022. The number and per- centage of tests were estimated from data extracted and estimation of costs was performed based on the currently recognized reimbursement from the National Health System. Results: Increased use of Gene Expression Profiling, performed on 4,54% of BC cases in 2022, and Next Generation Sequencing, performed on 42% NSCLC cases in 2022, led to higher average institution costs per patient (54% and 140% rise, respectively). This shift to molecular testing has reduced single gene testing in NSCLC, causing a 58% drop in RT-PCR and 50% decrease in IHC predictive tests. Conclusion: The paradigm shift in the assessment of BC and NSCLC cases due to the introduction of molecular tests changed the landscape of pathology departments from an organization and economic point of view. The integration of different data sources thanks to digital pathol- ogy and LIS dashboards allowed us to track the dynamic changes of this precision oncology transition.