ECP 2023 Abstracts

S308 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 automatic workflow to annotate the somatic variants (SNVs, indels, copy number variations and fusions). IHC for MMR and p53 proteins was also performed in all the cases. Results: All the cases were not pathogenic for MMR and not-mutated for p53. All the cases were evaluable for NGS; we detect allelic variants in POLE and TP53 genes in 29.0% and 41.0% of the cases, respectively. CNVs and additional SNVs in crucial genes (PIK3CA, PTEN, among other) were present in 76.5% of the tumours analysed. We also detect TP53 mutations in patched p53-positive cases (p<0.05). Conclusion: NGS gives added value to gene-to-gene/protein-to-protein analysis because it allows the detection of extra variants of possible clinical value. NGS also allows to detect unexpected TP53 mutations in those cases with patched TP53-positive expression. E-PS-15-015 Comparison of diagnostic coverage of RET fusion partners by vari- ous RNA-based assays M. Gupta*, A. Mota, I. Simon, J. Cazier *Eli Lilly, United Kingdom Background & objectives: RET fusions are actionable in non-small cell lung cancer (NSCLC) and papillary thyroid cancer (PTC). Design of different gene-panels affects their sensitivity to detect these fusions. We compared different RNA panel designs and their ability to detect RET fusion partners. Methods: We performed in silico comparison of RNA-based next-generation sequencing (NGS) panels and PCR based assays against a catalogue of known RET gene fusion partners. The panels included TSO500, Archer FusionPlex (Lung and Pan-solid tumour), Oncomine assays (Focus, Precision, Comprehensive, Comprehensive Plus and Dx Target Test) and PCR based assays from Biocartis and AmoyDx. Results: The results show a descriptive analysis of the specific RET - fusions and their partners that can be detected in NSCLC, PTC and other tumour types by each of the panels described above. Only a couple of fusion partners constitute the significant majority of RET - fusions. Therefore, we also present the proportion of known fusions that each technology can detect (i.e. sensitivity by design). Conclusion: This analysis determines the ability of different RNA- based panels to detect different RET fusions and their partners. These findings may provide clinical laboratories with additional information on the limitations of each assay for different tumour types. Funding: This project was funded by Eli Lilly. E-PS-15-016 Feasibility and impact of retrospective testing for RET fusions and other actionable biomarkers not previously tested in non-small cell lung cancer cases: an experience from England M. Gupta*, J. Bradbury, H. Sanna, S. Forrest, S. Taylor, C. Felix, F. Carter, C. Escriu, S. Brown, D. Bury, J. Gosney, M. Powari, M. Evans *Eli Lilly, United Kingdom Background & objectives: Non-availability of biomarker testing in advanced/metastatic non-small cell lung cancer (mNSCLC) limits access to targeted treatments for many patients. Here, impact of spon- sored retrospective testing for biomarkers not previously tested was explored, including identification of new patients for treatment. Methods: Gene-fusions were tested for RET, NTRK1/2/3 and METex14 skipping where patients were alive at the time of analysis and had sufficient quality and quantity of archived tissue available. Cases with previously identified actionable biomarkers were excluded. All testing was performed on Idylla GeneFusion Assay at five participating centres and, where needed, reconfirmed by next-generation sequencing (NGS) as per local protocols. Results: Of the 423 cases tested to date, Idylla assay was success- ful in 405 (95.7%). The testing identified 15 new biomarker positive cases, including 3 for RET and 12 for METex14. Confirmation through NGS is in progress for one and could not be completed in three oth- ers because of different reasons. Two patients have already received a targeted treatment. Importantly, this project enabled two centres to establish prospective testing for all routine cases. Additionally, one cen- tre took the opportunity to test the blocks pulled out from the archives for KRAS in parallel. Fifteen KRAS positive cases were identified, including 8 with the actionable G12C mutation. Conclusion: This feasibility study identified new patients for targeted treatments that would have been missed otherwise and emphasises the need for timely broad testing of genomic drivers in mNSCLC . It also increased awareness of biomarkers and local testing pathways among the healthcare staff, and motivated one centre to evaluate two different testing pathways. The project also catalysed dialogue between the oncologists, pathologists and laboratory staff, and the experience helped establish prospective testing at two centres. Funding: The project was sponsored by Eli Lilly and Company E-PS-15-017 Implementation of a multidisciplinary molecular tumourboard (MTB) L. Häberle*, S. Labuhn, M. Schlensog, W. Goering, K. Horny, S. Redler, I. Esposito *Institute of Pathology, University Hospital Duesseldorf, Germany Background & objectives: With high-throughput sequencing becom- ing more and more readily available and precision medicine on the rise, molecular tumour boards (MTBs) represent a pivotal tool in translating molecular findings into patient management. Methods: In July 2022, a multidisciplinary MTB was implemented at our university hospital, including cancer patients in last-line or near- last-line therapy, patients with rare cancers, and patients with initial cancer diagnosis at 50 years or younger. Next generation sequencing (NGS)-based molecular diagnostics is performed for all tumours. All cases are systematically documented and followed-up. Results: Between July 2022 and April 2023, 57 case presentations (56 individual patients) were documented at 19 online MTB conferences. Most cases were gastrointestinal cancers including hepatopancreatico- biliary cancers (43%), followed by urological (21%) and gynaecological (18%) cancers. Possible targets for therapy were detected in 55% of cases. Off-label therapies were recommended in 36%, inclusion into therapy studies in 18%, and EMA-approved therapies in 16% of cases. Conclusion: MTBs are a useful tool to guide therapy of cancer patients and facilitate access to therapy studies and off-label therapies. Follow- up data will be collected to evaluate adherence to MTB recommenda- tions and patient outcomes. E-PS-15-018 Squamous cell carcinoma of the lung with microsatellite instability in a patient with Lynch syndrome: a case report E. Haddad*, B. Bottet, P. Thiebaut, S. Morin, H. Dreyfus, E. Vanier, C. Vincent, H. Sobol, F. Marguet, J. Baste, F. Guisier, J. Sabourin, N. Piton *CHU Rouen, France Background & objectives: A 68 year old man with a history of colo- rectal cancer at age 36 (with recurrence at age 56) and a family history of cancers. A germline pathogenic mutation of MLH1 confirmed the Lynch syndrome. Methods: In 2022, as part of the follow-up of his colon cancer, a CT- scan was performed, retrieving a nodule of the right lung. A biopsy revealed a squamous cell carcinoma, that has been surgically treated. IHC showed a loss of MLH1 and PMS2 expression in tumour cells.