ECP 2023 Abstracts

S137 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 be significantly high in LN patients as compared to those without LN. Among these indices RDW & PLR were independent predictors of renal involvement. These findings suggests that these indices may be used as cost-effective and non-invasive potential markers for predicting renal involvement in SLE patients. PS-26 | Poster Session Uropathology PS-26-001 An algorithmic pattern-based practical approach to the new WHO classification of renal cell tumours: emphasis on kidney biopsy specimens M. Alzamora*, M. Hanbazazh, Â. Rodrigues, J. Loureiro, R. Henrique *IPO-Porto, Portugal Background & objectives: Presently, renal cell tumours (RCT) pose significant clinical challenges, warranting accurate biopsy-based diag- nosis. We propose a practical approach to the 2022 WHO classification established upon morphology and immunohistochemistry (IHC), test- ing the algorithm’s performance in paired kidney biopsies and surgical specimens. Methods: As per the WHO Classification of Urinary and Male Geni- tal Tumours 5th edition (2022), we reviewed literature to develop an algorithmic practical approach to RCT classification based on common morphologic features and distinct IHC profiles. We identified consecu- tive RCC cases spanning 2004-2022 through a query of internal records and compared diagnostic performance in biopsies and corresponding resection specimens. Results: Overall, we identified 160 eligible RCT cases and reviewed their diagnoses in light of the 2022 WHO classification using the pro- posed algorithm. The first discriminator consisted of five main mor- phological categories: clear cell tumours, eosinophilic cell tumours, tumours with a papillary pattern, tumours with a cystic pattern, and high-grade infiltrating tumours. Some tumours, such as clear cell RCC and MiTF-Translocation RCC depicted overlapping features across categories. IHC profiles and molecular techniques were particularly important for diagnosis in challenging cases, especially eosinophilic cell and high-grade infiltrating tumours. Conclusion: Accurate RCT classification provides clinically relevant information, aiding in patient management and improving communica- tion between pathologists and clinicians. We provide a practical and accurate framework for RCT classification based on the new criteria from the 2022 WHO Classification of Urologic Tumours, facilitating its widespread implementation. This approach may be particularly valuable for diagnosing kidney tumours in biopsies and may improve patient management. Overall, the proposed algorithm could improve accuracy and reliability of pre-operative RCT diagnosis to guide clini- cal decision-making. PS-26-002 Diagnostic spectrum of tumours developing in native kidneys of renal transplant recipients G. Aydogan*, B. Sarsik Kumbaraci, K.E. Ergun, B. Goktepe, A. Celtik, S. Sen *Ege University Faculty of Medicine, Department of Pathology, Turkey Background & objectives: The risk of developing de novo malignancy is high in organ transplant recipients receiving long-term immunosup- pressive therapy. Although skin and hematopoietic neoplasms are com- mon in general, tumours in native kidneys are also described. Methods: At our centre, 17 native nephrectomy of 14 patients who under- went kidney transplantation between 1989 and 2019 were examined. Three patients had bilateral nephrectomy. Twenty-one renal tumours detected in native kidneys of these patients were re-evaluated according to World Health Organization (WHO) 2022 renal tumours classification system. Results: In this study of 14 patients, of which two (14%) were female and twelve (86%) were male. The mean age of the patients was 51 years (range=14-75). The mean interval between transplantation and tumour diagnosis was 88 months (range=1-312). Histologically, these tumours were classified as follows; five (5/21,24%) papillary renal cell carci- noma (RCC), two (2/21,10%) clear cell RCC, two (2/21,10%) acquired cystic disease associated RCC. The other six tumours were TFE3-rear- ranged RCC, chromophobe RCC, clear cell papillary renal cell tumour, low-grade oncocytic tumour, papillary tumour with reverse polarity (RP-PT), and metanephric adenoma. The five (5/21,24%) tumours were in the morphology of renal papillary adenoma. One tumour could not be classified. Conclusion: The incidence of malignancy has increased in kidney transplant recipients. As a result, the risk of tumour development in the native kidneys is high. Therefore, clinical follow-up of native kidneys is extremely important. PS-26-004 IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma Y.M. Cho*, S.U. Jeong, J. Park, S.Y. Yoon, H.S. Hwang, H. Go, J. Lee, G. Jeong, H. Lee *Asan Medical Center, University of Ulsan College of Medicine, Republic of Korea Background & objectives: VEGF tyrosine kinase inhibitors (TKIs) have been the standard of care for metastatic clear cell renal cell carci- noma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory due to drug resistance to the TKI therapy. Methods: To define the TKI-resistance mechanism for TKI-resistant ccRCC, an integrative differential gene expression analysis was per- formed using paired tumour samples harvested at pre- and post-TKI treat- ment periods from 10 ccRCC patients and a public dataset. Sunitinib- resistant RCC cell lines were established and used to test their malignant behaviours of TKI resistance through in vitro and in vivo studies. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher prolifera- tive ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 over- expression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the TRAF6 and MAPK/AP-1 pathways. Conclusion: These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC. This work is funded by the Ministry of Science, ICT and Future Plan- ning (2019R1A2C1088246) and a grant (2022IL0018-1) from the Asan Institute for Life Sciences, Asan Medical Centre, Seoul, Korea. PS-26-005 Deep learning diagnosis of renal cell carcinoma using the largest dataset of whole slide images Y. Chong*, K. Yim, B. Kim, S. Jung, H. Shin, Z. Xu, S. Lim, M. Alam, Y.J. Choi *The Catholic University of Korea, Republic of Korea