ECP 2023 Abstracts

S309 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 MSI was confirmed by PCR amplification of tumour microsatellites, with comparison of normal tissue. Results: Lynch syndrome is due to constitutional mutations impair- ing the mismatch repair system, which result in tumour microsatellite instability. Patients with this condition are at a high risk of developing colorectal, uterine, ovarian, stomach, small bowel, pancreatic, kidney and brain cancers. However, the risk of lung cancer is considered the same as in the general population. In the literature, 3 cases of lung dMMR adenocarcinoma in patients with Lynch syndrome, including a Muir-Torr syndrome. In our patient, we rulled out the hypothesis of the lung metastasis of an urothelial carcinoma, which belongs to the spectrum of Lynch syn- drome, by the microscopic appearance of the tumour and the lack of GATA3 expression. Conclusion: dMMR status is a strong predictive biomarker for the efficacy of immune checkpoint inhibitors. Interestingly, a recent study reported a durable response to toripalimab in a dMMR squa- mous cell cancer of the lung. This must lead us to discuss immuno- therapy in case of recurrence of this squamous cell carcinoma of the lung in our patient. We report here the first case of a dMMR squamous cell carcinoma of the lung in a patient with Lynch syndrome. E-PS-15-019 Whole-exome sequencing of brain metastases and paired primary tumours of small cell lung carcinoma – preliminary results K. Heß*, F. Kellers, A. Kuenstner, N. Reimer, S. Fliedner, H. Busch, L. Bastian, C. Röcken, B. Konukiewitz *University Medical Center Schleswig-Holstein, Campus Kiel, Depart- ment of Pathology, Kiel, Germany Background & objectives: The process of brain metastasis of small cell lung cancer (SCLC) is poorly understood. The project aimed to compare the brain metastases of SCLC and their primary tumours using Whole Exome Sequencing (WES). Methods: WES was performed on formalin-fixed, paraffin-embedded tissue from 11 patients, including paired primaries and brain metastases from 5 patients. DNA was analysed using high-throughput sequencing on an Illumina sequencer. Data processing was performed with the "MIRACUM-Pipe" workflow and the OncoKB cancer gene list system. Cancer-relevant mutations were identified after comparison with the COSMIC database. Results: The most frequently observed genetic aberrations were non- sense mutations, missense mutations, or deletions of TP53 (n=9; 82%) and RB1 (n=7; 64%). Alterations in the Notch signalling pathway were detected in the primary tumours and also in the brain metastases by mutations in NCOR1, CREBBP, and NOTCH1. In contrast, KDM5A mutations have only been detected in the primary tumours. Further- more, VEGFR1 and RNF213 mutations were identified as angiogen- esis-regulating genes, and AFND and ABL2 as modulators of cell- cell contacts and extracellular matrix. Besides VEGFR1 (n=2; 18%), BRCA2 (n=4; 36%) could be identified as a possible therapeutic target in primary tumours and brain metastases. Conclusion: In the comparative analyses between SCLC and brain metastases, gene mutations considered driver genes (TP53 and RB1) of neuroendocrine carcinoma were detected, as well as gene muta- tions associated with angiogenesis, tumour growth, and invasion that presumably contribute to the process of metastasis. In addi- tion, our results suggest potential therapeutic options for a subset of SCLC metastases, especially with regard to VEGFR1 and BRCA2/ PARP inhibitors. Funding: The author Katharina Hess received funding from "Familie Mehdorn foundation". E-PS-15-020 Homologous recombination deficiency analysis by panel NGS in 148 penile squamous cell carcinoma samples J. Hojný*, M. Kendall Bártů, E. Krkavcová, R. Michálková, J. Hrudka *Department of Pathology, First Faculty of Medicine, Charles Uni- versity and General University Hospital in Prague, Czech Republic Background & objectives: Penile squamous cell carcinoma (pSCC) is rare tumour with limited understanding of its genomic background. We investigated the potential of homologous recombination deficiency (HRD) as a prognostic and/or predictive marker in pSCC, considering its recent success in various cancer types. Methods: We analysed a cohort of 148 histologically confirmed inva- sive pSCC cases. A panel of 359 gene-targets (1.16 Mbp) was used for capture NGS. The data were bioinformatically processed with CLC Genomics Workbench software, and the HRD score was calculated as the sum of "Loss of Heterozygosity," "Large-scale State Transitions," and "Telomeric Allelic Imbalance” events and compared to optimized HGSC cut-offs. Results: The overall results of HRD analysis showed high scores compared to the cut-offs optimized for HRD-high HGSC samples, especially in low-quality samples. Out of 148 pSCC samples, 36 were evaluated as HRD-high, of which 26 had limited quality and/or cover- age. Therefore, 58/148 samples with coverage <400x were discarded, and the HRD score was recalculated. The final results showed an aver- age pSCC HRD score of 51 (median = 51; minimum = 20; maximum = 80). Out of the final 90 samples, 10 were evaluated as HRD-high (11%; HRD>=65), 63 as HRD-intermediate (70%; HRD>42 and <65), and 17 as HRD-low (19%; HRD<=42). Conclusion: Our HRD analysis of pSCC revealed relatively high levels of HRD score with potential treatment implications for 11% of patients, compared to standardized HGSC calculation. However, further cor- relation with molecular profiles and histopathological pSCC subtypes is needed to fully evaluate the prognostic and/or predictive value of HRD status in pSCC (currently in progress). Additionally, the observed limitations of small NGS panels combined with low-quality samples in HRD calculation should be considered in future NGS studies. Funding: This work was supported by the Ministry of Health, Czech Republic (MH CZ AZV NU21J-03-00019 and DRO-VFN 64165) E-PS-15-021 Revolution in pathology, no more formalin fixation! Reduced DNA deterioration in five years in nonfixed tissues processed with super- critical CO2 compared to formalin fixation M. Hoogland*, N. van der Horst, A. Knol, M. Niemantsverdriet *Isala, The Netherlands Background & objectives: Toxic, DNA damaging formaldehyde was banned, except in the medical sector where it is routinely used during pathological analysis. The objective was to compare long term effect on DNA quality of formalin fixation to processing tissues using non- toxic supercritical CO2. Methods: Fresh human tissues were collected and split in 2018. Of each tissue, one sample was processed using conventional method (FFPE, Formalin Fixed Paraffin Embedded). The second sample freshly processed in non-toxic supercritical CO2 (NFPE, Non Fixed Paraffin Embedded). As pilot, five years after storage in the archive, of four selected tissues DNA parameters were compared between FFPE and NFPE processing. Results: In a 4-tissue pilot experiment (lung, kidney, mamma and liver), five years after embedding in paraffin and archive storage; DNA parameters of NFPE samples were typically better compared to