ECP 2023 Abstracts

S133 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Conclusion: We devised a novel method to determine genomic insta- bility for characterizing consequence of HRD using OCA Plus, which was developed for fast CGP of cancer FFPE samples to aid research into precision oncology. By combining genomic instability assessment with DNA repair pathway analysis such as mutations in BRCA1/2 and other genes in HRR pathway, OCA Plus will support research into the mechanisms underlying HRD. PS-24-006 17p13 deletions are a feature of p53 null phenotype in urothe- lial bladder cancer and is associated with an aggressive tumour phenotype M. Kluth*, M. Hitzschke, H. Plage, M. Lennartz, N. Blessin, A.H. Marx, M. Fisch, M. Slojewski, T. Ecke, S. Koch, G. Sauter, T. Klatte, T. Schlomm, D. Horst, H. Zecha *Institute of Pathology, University Medical Center Hamburg-Eppen- dorf, Germany Background & objectives: 17p13 deletions including p53 and other genes represent a common cause for reduced/lost p53 function in tumour cells. In this study, we analysed the impact of TP53 deletions and p53 expression on tumour aggressiveness and patient prognosis in urothelial carcinoma. Methods: 17p13 copy number status was analysed by fluorescence in-situ hybridization (FISH) on more than 2,500 urothelial bladder carcinomas in a tissue microarray format. 17p13 deletion data were compared to p53 expression data measured by immunohistochemistry (IHC) which were available from a previous study. Different types of p53 alterations were compared with tumour phenotype and clinical outcome data. Results: 17p13 deletions occurred in 23% of 2,185 analysable carci- nomas. The fraction of tumours with 17p13 deletions increased from pTa G2 low (9%), to pTa G3 (24%, p<0.0001). In muscle-invasive carcinomas, 17p13 deletions were associated with advanced pT stage (p=0.0246), but unrelated to patient prognosis (p>0.5). 17p13 dele- tions were significantly related to p53 immunostaining (p=0.0375). 17p13 deletions were most common in tumours with complete lack of p53 staining (31%), which supports the concept that these tumours have a complete loss of p53 function (p53 null phenotype). 17p13 deletions were also increased in tumours with high p53 staining (26%). Conclusion: 17p13 deletions were most commonly seen in p53 nega- tive cancers, supporting their role as a cause for p53 null phenotype in urothelial cancer. The association of 17p13 deletions with high grade and advanced pT stage may reflect increasing genomic instability going along with stage and grade progression. PS-24-007 Performance of microsatellite instability detection using Elio Tis- sue Complete and Idylla platforms in endometrial cancer J. Lobo*, M. Hanbazazh, D. Shimoga Chandrashekar, S. Harada, A.C. Mackinnon *Portuguese Oncology Institute Porto, Portugal Background & objectives: Low-level microsatellite instability (MSI) phenotypes are common in endometrial cancer (EC) and may be missed with molecular-based testing platforms. We aim to assess the MSI detection performance of the Idylla and the FDA-cleared Elio Tissue Complete (ETC) platforms. Methods: Immunohistochemistry (IHC) for mismatch repair (MMR) proteins was used as the gold standard for defining MMR status. Tumour DNA was extracted from FFPE tissue blocks, and MSI test- ing was performed using the Idylla (Biocartis, Mechelen, Belgium) and ETC platforms (PGDx/labcore, Baltimore, MD). Performance was assessed by evaluating concordance between MMR IHC, Idylla, and ETC. Results: Thirty EC cases were included: 21 MMR deficient (19 MLH1/PMS2, 1 MSH2/MSH6 and 1 MSH6 deficient) and 9 MMR proficient. 20 of 21 cases showed MSI by Idylla and ETC. 1 discord- ant case (with loss of MLH1/PMS2) was missed by Idylla and ETC using vendor-defined thresholds for MSI detection. Evaluation of the ETC NGS data demonstrated low-level MSI characterized by loss of 1 nucleotide in 15 of 66 microsatellite tracks (23%). Conclusion: Despite widespread use, PCR analysis for determining MSI has several limitations, and ECs with low-level MSI phenotypes represents a major diagnostic challenge. Increasingly, MSI testing is a component of pan-solid tumour NGS panels allowing simul- taneous determination of complex molecular signatures (e.g., MSI, tumour mutation burden) and detection of somatic variants. Despite the inherent challenges with MSI detection across different tumour types, methods for NGS-based MSI testing are reliable provided labs carefully establish and validate interpretation criteria. PS-24-008 Prognostic significance of epithelial-mesenchymal transition (EMT) markers in stage I-III colorectal cancer A. Matly*, P. Hatthakarnkul, A. Ammar, M. McFarlane, J. Quinn, N. Maka, J. Park, K. Pennel, J. Edwards *University of Glasgow, United Kingdom Background & objectives: Epithelial-mesenchymal transition (EMT) is an important process in the development of metastases and colorectal cancer (CRC) progression. However one marker alone is not sufficient to identify the process. This study assessed expression of six EMT markers in CRC human specimens. Methods: The study cohort consisted of 787 stage I-III CRC patient specimens. Immunohistochemistry was utilised to determine expression of E-cadherin, β-catenin, Snail, Twist 1, ZEB 1, and SOX 9 in a tissue microarray and expression was assessed using the weighted histoscore method. Full sections from the same cohort were utilised to perform transcriptomic analysis using TempO-Seq technology, Bioclavis. Results: High expression of Snail (P=0.007) and Twist1(P=0.031) was associated with decreased cancer-specific survival (CSS). When β-catenin and E-cadherin expression were combined, low expression of β-catenin and high expression of E-cadherin associated with good prognosis (P=0.0027), inflammation (p = 0.05), increased memory T-cells within the stroma (p = 0.025), and tumour invasive margin (p = 0.04). Cox-regression analysis demonstrated when combined with known clinical variables, the combined β-catenin E-cadherin score was independently associated with CSS (HR 2.379 95% CI 1.435–3.942, p < 0.001). Highest differentially expressed genes were CTNNB1 (β-catenin), Myc, NOTCH1 and TCF7 and gene set enrich- ment analysis demonstrated WNT β-catenin signalling and EMT gene sets were up-regulated. Conclusion: The combined β-catenin and E-cadherin score stratifies patient’s survival and associates with factors relating to metastasis. This combined β-catenin, E-cadherin score could be used to identify patients at risk of micro metastasis, who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade ther- apy. Gene set enrichment analysis revealed that CTNNB1 (β-catenin) and TCF7 upregulation associated with poor survival in the cohort identifying these genes as promising candidates for targeted therapy and are worthy of further investigation. Funding: Bowel cancer UK PS-24-009 Next Generation Sequencing bile study as a pathological diagnostic tool for early diagnosis of cholangiocarcinomas M.d.R. Mercado Gutierrez*, I. Amat, M. Arechederra, M. Rullan, P. Azcue, I. Fernández De Los Reyes, D. Guerrero-Setas, B. Carmen, M. Avila, A. Córdoba