ECP 2023 Abstracts

S311 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 E-PS-15-025 CCND1 but not DOG1 is associated with an aggressive phenotype of urothelial bladder cancer M. Kluth*, A. Frericks, H. Plage, M. Lennartz, N. Blessin, M. Slojewski, T. Ecke, S. Koch, R. Simon, G. Sauter, T. Klatte, T. Schlomm, D. Horst, H. Zecha, K. Jansen *Institute of Pathology, University Medical Center Hamburg-Eppen- dorf, Germany Background & objectives: DOG1 and CCND1 are jointly localized on 11q13.3, a frequently amplified region in different tumours. Both genes are potential candidates for the management of targeted tumour therapies. The prognostic role of DOG1 and CCND1 alterations are unknown in bladder cancer. Methods: DOG1 expression was analysed by immunohistochemistry and CCND1 amplification by fluorescence in situ hybridization on tis- sue microarrays containing more than 2,700 urothelial bladder carci- nomas, including 636 patients that underwent radical cystectomy for muscle-invasive disease. Results: CCND1 amplification occurred in 15.5% of the 1,880 ana- lyzable carcinomas. Amplification rate increased from pTa G2 low (2.4%) to pTa G2 high (16.5%), and pTa G3 (27.8%; p<0.0001). It was 18.9% in muscle-invasive pT2-pT4 carcinomas. Amplification was unrelated to phenotype and prognosis. DOG1 positivity occurred in 27.0% of 2,515 analyzable carcinomas, including 4.1% with strong staining.DOG1 positivity was more frequent in pTa (36.2%) than in pT2-4 carcinomas (22.8%; p<0.0001) but unrelated to phenotype and prognosis in pTa and pT2-4 carcinomas. Strong DOG1 immunostaining was linked to CCND1 amplification (p<0.0001). Tumours with strong DOG1 positivity had CCND1 amplification in 45.0% while only 12.2% of amplified cases showed strong DOG1 staining. Conclusion: CCND1 is amplified in about 20% of invasive urothelial bladder cancers and results in high level DOG1 expression in about 50% of cases. CCND1 amplification correlates with a higher grade in pTa tumours. Neither CCND1 amplification nor DOG1 expression are related to patient prognosis. E-PS-15-026 Tumour mutation burden analysis in solid tumours Y.B. Kök*, S. Erdamar Çetin, M.C. Yakıcıer, A. Erşen Danyeli, F. Tokat, Ü. İnce *Acıbadem Mehmet Ali Aydınlar University, Faculty of Medicine, Department of Pathology, Turkey Background & objectives: Tumour mutation burden (TMB) is a meas- ure of the somatic mutations in tumour genome. The prognostic role of TMB in solid tumours is debated. This is the first study in Turkey to document TMB in solid tumours with clinicopathologic characteristics. Methods: DNA and RNA was isolated from FFPE tumour tissues; then comprehensive genomic profiling (Trusight Oncology 500assay) of more than 500 genes whose mutations are known to participate in carcinogenesis were searched for including insertions, deletions, single nucleotide variations, amplifications, fusions or alternative splicing, using NOVASEQ 6000 SYSTEM, ILLUMINA platform and PERIANDX software. Threshold for TMB-high was accepted as >10mutation/megabase. Results: Of 142 patients, mean age:56,3(1-87) and female/male:73/69, with solid tumours evaluated for TMB, 45(31,7%) were found to have high TMB. In TMB-high patients, mean age was 60,6 and female/ male ratio was 17/28. The most common site in TMB-high group was lung(n=22; 67% of total lung cancers), followed by colon(n=6), uterus (n=4) and ovary(n=4), stomach(n=3), skin(n=1; 11% of total melano- cytic lesions), adrenal gland(n=1), mediastinum(n=1), breast(n=1), bladder(n=1), gallbladder(n=1). Microsatellite instability was found in 5 cases (3,5% of total) in TMB-high group(11%) whereas there was none in TMB-low group. There was not any correlation between TMB level and age, gender and PD-L1 expression. Conclusion: This is a preliminary study on TMB analysis of solid tumours. Similar to the literature, TMB levels varies across different tumour types. In our study, highest levels were seen in non-small cell lung cancer, probably due to heavy smoking habbit in our country. On the other hand, melanocytic skin tumours showed lower TMB levels in our series compared to other studies. Considering its importance for immunotherapy, standardization of TMB is getting more important. E-PS-15-027 Homologous recombination deficiency analysis in solid tumours Y.B. Kök*, S. Erdamar Çetin, A. Erşen Danyeli, F. Tokat, M.C. Yakıcıer, Ü. İnce *Acıbadem Mehmet Ali Aydınlar University, Faculty of Medicine, Department of Pathology, Turkey Background & objectives: Homologous recombination deficiency (HRD) is a type of DNA repair deficiency, which may give rise to malignancies with increased sensitivity to platinum-based chemother- apy and PARP inhibitors. In this preliminary study, we analysed of HRD status for various solid tumours. Methods: This is a retrospective study of solid tumours for which HRD panel studies were requested by the clinic. DNA was isolated from FFPE tumour tissues, then NGS scanning for variations in genes ATM, BARD1, BRCA1/2, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B/C/D, RAD54L, TP53 was performed using MiSeq SEQUENCING SYSTEM, ILLUMINA platform and SOPHiA-DDM- V-5.10.12.1 software. Results: HRD was analysed in 74 patients with malignant solid tumours. Mean age was 60,7 (39-78) and male/female ratio was 24/50. Tumours of various origins included ovary(n=28), prostate(n=17), pancreatobiliary system(n=7), breast(n=5), endometrium(n=3), colon(n=3), peritoneum(n=2), oesophagus (n=1), fallopian tube(n=1), while 7 carcinomas were of unknown origin. 54 cases showed at least 1 pathogenic variation in the panel: TP53(n=40), BRCA1(n=10), ATM(n=5), CHEK2(n=4), BRCA2(n=3), RAD51(n=2), BARD1(n=2), PALB2(n=1), CDK12(n=1). 29 (39%) cases showed mutations only for TP53. In 25 (34%) cases evaluated as HRD (excluding TP53-only cases), rates according to organ distri- bution were as follows: Ovary:39%(n=11), prostate:53%(n=9), pan- creatobiliary system:29%(n=2), endometrium:33%(n=1), unknown origin:29%(n=2). Three of these HRD cases (relatively 12%) showed mutations in two different HRD-genes. Conclusion: The HRD rates shown in tumours are reported in a wide range in the literature, and our results (34%) also fell within this range. While pioneering studies in HRD-targeted therapies centred around ovary and breast, it has become recognized day by day in other organs, such as prostate and pancreas. In addition, the focus on searching for BRCA mutations is giving way to multi-gene panels containing genes that have been shown or predicted to contribute to therapy implications. E-PS-15-028 Different miRNA involvement in rectal neuroendocrine tumours showing either common mutation or high mitotic index: a pilot study M.J. Kwon*, S.Y. Kang, H.S. Kang, H.Y. Park, N.Y. Kim, M. Hong *Hallym University Sacred Heart Hospital, Republic of Korea Background & objectives: Neuroendocrine tumours (NETs) are uncommon, heterogeneous groups of neoplasms with malignant poten- tial. They need to determine the frequency of clinically and patho- logically relevant mutations and miRNA expressions in rectal NETs to identify morphologic profiles related to prognosis and behaviour.