ECP 2023 Abstracts

S15 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Background & objectives: There is a limited number of studies inves- tigating GATA3 expression in eosinophilic renal tumours. We aimed to assess GATA-3 expression in newly defined eosinophilic renal tumours that have overlapping morphological features between oncocytoma and chromophobe renal cell carcinoma (CRCC). Methods: Thirty eosinophilic tumours from 29 cases that have radi- cal/partial nephrectomy or needle biopsy materials between 2021 and 2023 have been reevaluated retrospectively by their morphological and immunohistochemical findings. The morphological features and expressions of GATA3, CK7, CK20, vimentin, SDHB, FH, HMB45, Melan A, and CD117 were evaluated. Results: The mean age was 58,17±17,07 years (range; 13-87) with a slight predominance of men over women (1.2:1 ratio). There were 13 (45%) CRCCs, 8 (28%) oncocytomas, two (7%) eosinophilic solid cystic RCCs (ESC-RCC), and three (10%) low-grade oncocytic tumours (LOT). Papillary tumour with reverse polarity (RP-PT) coexisted with one of the LOT cases. The other three tumours were SDHB-deficient RCC, FH-deficient RCC, and TFEB-rearranged RCC. LOTs, SDHB-deficient RCC, FH-deficient RCC, and RP-PT showed diffuse, 10 of 13 CRCCs, and 2 of 8 oncocytomas showed focal GATA3 positivity. SDHB-RCC, FH-RCC, TFEB-RCC, ESC-RCC, and onco- cytomas didn’t express CK7. The newly identified LOT and RP-PT (provisional entity) showed GATA3 and CK7 expressions. Conclusion: Morphological similarity of CRCC, oncocytoma, and newly defined eosinophilic tumours in nephrectomy and kidney needle biopsy materials can cause diagnostic problems. Our results show that diffuse CK7/GATA-3 coexpression contributes to identifying eosinophilic renal tumour types in routine practice. Awareness of this immunohistochemi- cal profile in eosinophilic renal tumours may help to avoid misdiagnosis. OFP-04-004 Investigating the prognostic value of invasive cribriform gland size and percentage in grade group 2 and grade group 3 prostate adenocarcinoma E. Tekin*, N.S. Şeker, A. Ozen, M.F. Açıkalın, C. Can, E. Çolak *Eskişehir Osmangazi University, Faculty of Medicine, Department of Pathology, Turkey Background & objectives: Gleason scores guide clinical management in prostate adenocarcinoma. Cribriform glands are linked to poorer outcomes. Our study aims to assess the prognostic role of invasive cribriform gland size and percentage in low-intermediate risk group adenocarcinomas. Methods: Our study enrolled 177 male patients with Grade Group 2 and 3 prostate adenocarcinomas. All cases were re-evaluated and recorded clinical and pathological data. The largest invasive cribri- form gland was identified, and its diameter measured. P63 was used as a basal marker for all cases. Results: The mean age of the patients was 67.8 years. Lymph node metastasis was not detected in cases without cribriform pattern, whereas it was noted in 22.5% of cases with cribriform pattern (p=0.014). The mean percentage of cribriform glands and the mean largest invasive cribriform gland size were significantly higher in cases with lymph node metastasis compared to cases without lymph node metastasis (34.3% - 2.98 mm vs. 17.5% - 1.98 mm, respectively; p<0.001 and p=0.003, respectively). Biochemical recurrence-free survival was significantly lower in cases with a maximum invasive cribriform gland diameter of >0.5 mm (p<0.001) and in cases with a cribriform pattern percentage of >10% (p<0.001). Conclusion: Mean cribriform gland sizes and percentages were significantly associated with more advanced pT status, a higher rate of extraprostatic extension, lymph node metastasis, biochemical recurrence, higher preoperative PSA values, surgical margin posi- tivity, and lower biochemical recurrence-free survival. Our findings suggest that a more aggressive clinical approach may be needed in grade group 2 and 3 cases with invasive cribriform glands larger than 0.5 mm and a cribriform gland percentage of >10% in prostate needle biopsies. Funding: Eskişehir Osmangazi University Scientific Research Project Unit OFP-04-005 Intraepithelial CD8+ cytotoxic T-cells are the main component of the immune tumour microenvironment that drive prognosis in muscle-invasive bladder cancer N. Blessin*, N.F. Debatin, E. Bady, T. Mandelkow, H. Samtleben, D. Horst, A.H. Marx, M. Fisch, M. Slojewski, T. Ecke, S. Koch, N. Adamini, G. Sauter, T. Schlomm, H. Zecha *Institute of Pathology, University Medical Center Hamburg-Eppen- dorf, Germany Background & objectives: Quantity and the spatial relationship of individual immune cell (sub)types can provide prognostic information in muscle-invasive bladder cancer. Methods: To study the prognostic role of different immune cell sub- populations in muscle-invasive bladder cancer, we stained 521 mus- cle-invasive urothelial bladder carcinomas with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry (mfIHC) in a tissue microarray format. A framework of neuronal net- works was trained and used for image analysis. Results: The identification of more than 300 different immune cell sub- populations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. 40 immune parameters showed prognostic significance in univariate analyses of which 15 were independ- ent from pT, pN, and histologic grade. The strongest association to clinical outcome was identified for intraepithelial CD8+cytotoxic T-cells (tAUC: 0.70) compared to all other 15 independent prognosis parameters (AUC: ≤0.68,0.039). Deeper spatial analysis revealed an increased expression levels of TIM3, CTLA-4 and PD-1 on CD8+ T cells that were located in the intraepithelial compartment. Furthermore, the cell-to-cell interaction profile of intraepithelial CD8+T-cells was dominated by intraepithelial dendritic cells as well as intraepithelial M1-macrophages. Conclusion: The intraepithelial CD8+T-cells that showed the high- est expression level of TIM-3, PD-1 and CTLA-4 and were strongly interacting with M1-macrophages as well as dendritic cells and repre- sented the strongest prognostic parameter in muscle-invasive bladder cancer. This can be explained by the fact that tumour cell destruction by CD8+cytotoxic T-lymphocytes through direct cell-to-cell-contacts represents the “terminal-end-route” of anti-tumour immunity. The strongest prognostic immune-factor –intraepithelial CD8+T-cells– can be measured straightaway in routine pathology as the CD8-labelling index using conventional bright field immunohistochemistry. OFP-04-006 Evaluation of PBRM1, PD-L1, CD31 and CD4/CD8 ratio as a predictive signature of response to VEGFR-TKI-based therapy in metastatic renal cell carcinoma (mRCC) patients with IMDC intermediate prognosis: results from the APAChE-I study M. Martini*, C. Ciccarese, V. Fiorentino, F. Pierconti, G. Tortora, R. Iacovelli, A. Ieni *Università di Messina, Italy Background & objectives: Current first-line (1L) therapy options for intermediate IMDC group mRCC patients (pts) are based on anti-angio- genic agent (VEGFR-TKI) and/or immunotherapy. No biomarkers (BM) for selecting the most effective regimen have been identified so far. Methods: Immunohistochemical expression of PBRM1, PD-L1, CD31, and CD4/CD8 ratio was evaluated on 156 histological samples of inter- mediate-risk mRCC pts treated withVEGFR-TKI monotherapy. Cox model was used to assess the correlation between BM and outcomes; PFS and OS were estimated by Kaplan-Meier method.