ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 patient clinicopathological parameters. Also, functional studies of growth, apoptosis, migration and invasion were conducted on PCa human cell lines with transient and permanent silencing of the B7-H3 protein. Results: High B7-H3 expression correlated with worse clinico- pathological patient features in intermediate and high risk PCa patients, including higher T stage (p<0.0001), perineural inva- sion (p=0.01) and lymph node spread (p=0.0006). Loss of B7-H3 expression did not affect prostate cancer cell growth or apoptosis in vitro. In contrast, there was significant decrease in migration and invasion with scratch wound assays, transwell migration assays and inverted transwell migration assays in vitro following sup- pressed B7-H3 expression in multiple human prostate cancer cell lines. RNA sequencing identified extracellular space chemotactic cytokines and their receptors, such as CCL2, CXCL1, CXCL8, CXCL6 and CXCL16 to be highly downregulated genes in PC3M cells with B7-H3 knocked out. Conclusion: B7-H3 protein is overexpressed in PCa making it a promising target for immunotherapies. Examining human tissue samples, we showed an association of B7-H3 expression and aggressive clinical features, including lymph node spread. In vitro experiments with acute and chronic loss of B7-H3 revealed an effect on migration and invasion. Future experiments are required to investigate the mechanistic downstream pathways of this phenotype and further evaluate the role of B7-H3 in metastasis in vivo. Funding: Cancer research UK PS-26-007 GATA-3 is a useful immunohistochemical marker to identify periprostatic paraganglia J. Gómez Trashorras*, M.d.l.Á. Betancor Santos, M. Conde Fer- reirós, S. Abdulkader Sande, A. Bellas Pereira, P. San Miguel Fraile, J. González-Carreró Fojón, J.A. Ortiz Rey *Hospital Álvaro Cunqueiro, Spain Background & objectives: Periprostatic paraganglia (PP) can be a pitfall leading to a misdiagnosis of prostatic carcinoma. Most of paragangliomas and pheochromocytomas are positive for GATA-3. To the best of our knowledge this fact has not been stud- ied in normal PP. Methods: Radical prostatectomy surgical specimens in which PP were observed with hematoxylin-eosin were selected for the study. Formalin-fixed paraffin-embedded sections were immunostained with a GATA-3 monoclonal antibody (clone L50-823) using an enzyme-conjugated multimer complex (OptiView DAB Detection Kit®, Ventana Medical Systems, Illkirch, France) in an automatic stainer (Benchmark Ultra®). Heat antigen retrieval was done in the automatic stainer. Results: Thirteen PP were found in twelve radical prostatecto- mies (8,1% of the total of the surgical specimens). PP ranged in size from 190 to 1140 μm, with a median dimension of 499,38 μm. They were located within the adipose periprostatic tissue in the middle region (10 cases, of which 8 were in the postero- lateral area and 2 were anterior); two at the base and one at the apex. 6 PP were on the right and 5 on the left side; one in the middle line and one was unknown. There was available tissue for immunohistochemistry in 10 cases, all of which showed intense and diffuse nuclear staining for GATA-3. Conclusion: PP have been found in radical prostatectomy specimens with a frequency similar to previously reported (around 8% of the cases). They are located in the periprostatic tissue, predominantly in the middle region and the posterolateral aspect of the prostate. A frequent clear cytoplasmic appearance of PP cells can lead to a misdiagnosis of prostate adenocarcinoma. GATA-3 is a useful immunohistochemical marker for the differential diagnosis as it is strongly positive in PP. PS-26-008 Prognostic value of tumour budding in urinary tract cancer: a meta-analysis R. SHI*, M.T.L. Tan, G.H. Lim, L. Zeng, P.H. Tan *Department of Anatomical Pathology, Singapore General Hos- pital, Singapore Background & objectives: Recently, tumour budding (TB) has been suggested as a strong prognostic marker in urinary tract cancer. The aim of this systematic review is to test the prognostic value of TB in urothelial cancer by a meta-analysis of previously published studies. Methods: We systematically reviewed the literature related to TB by using the databases of PubMed and Web of Science. The search was limited to publications in the English language up to and including December 2021. Results: There were 790 patients from 8 retrospective studies in which TB has been evaluated in urinary tract cancer. The meta-analysis of eligible studies revealed that TB is a significant prognosticator for progression free survival, with a risk ratio (RR) of 3.50 (95% confidence interval (CI) 2.01– 6.08; P < 0.001) in univariate analysis, and with a RR of 2.81 (95% CI 1.75–4.51; P < 0.001) in multivariate analysis; a significant prognosticator overall survival, with a risk ratio (RR) of 2.80 (95% CI 1.96– 3.99; P < 0.001) in univariate analysis, and with an RR of 1.02 (95% CI 1.01–1.03; P < 0.001) in multivariate analysis. Conclusion: We conclude that a high TB score is a promising prognostic marker of poor survival in urinary tract cancer. Because of its simplicity and high predictive power, TB is strongly recommended to be included in the routine pathology report of urinary tract cancer. PS-26-009 Enhanced TOLLIP expression confers poor prognosis in renal cell carcinoma A. Kowalewski*, D. Jaworski, J. Borowczak, M. Maniewski, P. Antosik, J. Durślewicz, M. Smolińska, D. Grzanka, Ł. Szylberg *Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland; Department of Tumour Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland Background & objectives: Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is exceptionally resistant to systemic therapies. TOLLIP protein is a regulator of immune responses. We explored the relationships between the clinical course of RCC and TOLLIP protein expression. Methods: The tissue microarray (TMA) cohort contained 95 cores of primary tumour, matched metastases and matched adjacent tis- sues derived from 32 RCC patients. The mean follow-up was 105 months. Immunohistochemical analysis of TOLLIP was performed on all tissue samples. TOLLIP expression was evaluated using the H-score and then analysed with patients’ clinical data. Results: All the examined samples showed cytoplasmic TOLLIP expression with the median value of 100 in primary tumours, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to S169