ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 transurethral resections (TUR) in retrospective studies. We aimed to validate ROL system on a prospective large mono-institutional series. Methods: From 2013 to 2020, we adopted ROL for all patients with pT1HGUC on TUR and collected clinico-pathological data. We employed a cut-off of 1 mm (or diameter of an objective 20x high-power field) to stratify tumours in ROL1 and ROL2, corre- sponding to one invasive focus or multiple foci extending together for <1 mm and for >1 mm, respectively. Results: A total of 229 confirmed pT1HGUC were analysed. Mean age was 73yrs, with male predominance (74.7%); 70 tumours showed multifocality (30.57%), 33 divergent differentiation (14.4%). Associated CIS and vascular invasion occurred in 14% and 9% of cases. ROL was feasible in all but one case (99.6%): 94 cases were ROL1 (41%) and 134 ROL2 (59%). At a median follow up of 23 months (IQR 12.33-38.5), 59 patients had recurrence (25.76%) and 37 progression (16%). ROL predicted progression in univariate (OR= 3.58, 95% CI 1.50-8.56; p=0.004) and multivariate (OR= 2.95, 95% CI 1.11-7.87; p=0.03) Cox regression analysis. At Kaplan-Meier estimates, ROL showed correlation with progression (p<0.01), but not with recurrence (p>0.05). Conclusion: Our results confirmed the strong predictive role of ROL system for progression in pT1HGUC on a large prospective series. The management of pT1HGUC patients is still a challeng- ing issue in urological practice, and depth and amount of lamina propria tumour invasion is a key prognostic variable. We foster the application of ROL system for substaging T1HGUC, a simple and feasible method alternative to pT1a/b that might identify high-risk patients and drive urological decision-making. OFP-05-009 Computational analysis of nuclear features as a grading tool for urothelial carcinoma I. Fahoum*, D. Rattner, A. Zubkov, A. Greenberg, O. Green- berg, R. Naamneh, V. Zemser-Werner, S. Tsuriel, R. Hagege, D. Hershkovitz *Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel Background & objectives: Tumour grade determines prognosis in urothelial carcinoma. The two-tiered classification of low and high grade is based on nuclear morphological features. The purpose of this study is to assess the value of computer-based image analysis tool for urothelial carcinoma grading. Methods: 400 images of urothelial tumours were graded by five pathologists and one uropathologist using a scale of 1 (lowest grade) to 5 (highest grade). A computer algorithm was used to segment the nuclei and to provide 40 morphometric parameters for each nucleus, which were used to establish the grading algorithm. Grading algorithm was compared to pathologists’ agreement. Results: In the training cohort 10 different nuclear parameters showed >85% agreement with the uropathologist’s score. All 10 parameters showed >85% agreement with the uropathologist’s score in the independent validation cohort. Three parameters showed 94.5% agreement in the validation cohort. The agreement of the pathologists with the uropathologist ranged from 88.5% to 97.5%. Unexpectedly, the parameter that was most associated with grade was the 10th percentile of the nuclear circumference, and high grade was surprisingly associated with lower 10th percentile nuclei, caused by the presence of more inflammatory cells in the high-grade tumours. Conclusion: Quantitative nuclear features could be applied to quantitate urothelial carcinoma grade. AI assisted grading systems could explore new nuclear parameters with better correlation to grade than those currently used. OFP-05-010 Tumour microenvironment immune markers associated with pathologic response to neoadjuvant pembrolizumab in muscle- invasive bladder cancer (Pure-01 trial: an open label, single arm, Phase II study) L. Cattaneo*, L. Carpenito, C. Napolitano, V. Lagano, I. Bersani, P. Giannatempo, A. Necchi, N. Nicolai, P. Biagio, M. Colecchia, G. Pruneri, R. Mortarini, A. Anichini *IRCCS Fondazione Istituto Tumouri, Italy Background & objectives: PURE 01 trial enrolled 143 patients who received 3 cycles of pembrolizumab (IO) every 3 weeks before radical cystectomy. We compared tumour-microenvironment immune markers expression in pre-IO TURB specimens in com- plete/major and non-responders to identify features associated with pathologic response. Methods: Immunohistochemistry expression of CD3, CD8, CD68-KP1, CD163, CD20, PD1, PD-L1, MHC-I, HLA-DR and Beta2-microglobulin on tumour cells and tumour- microenvironment was evaluated in 18 complete responders (CR: ypT0), 6 major responders (MR: ypTa/ypT1) and 19 non- responders (NR: ypT2/ypT3, N0 or N+) with a semiquantitative count of the positive cells percentage (0, 0%; 1, <25%; 2 , 25-50%; 3, 51-74%; 4, 75-100%). Results: Seven markers (CD8, stromal or tumour PD-L1, HLA-DR on tumour cells and B2M on tumour cells) were significantly more expressed (p value range: 0.001 to 0.048) on TURB lesions from responders (CR + MR) compared to non responders (N0 or N+). In addition to such markers, patients achieving a CR, compared to non responders, showed significantly higher expression of CD68 and CD163, of PD-1 on lymphocytes, as well as of tumour MHC-I molecules. Comparison of lesions from patients with CR vs MR revealed significant differences for CD3, CD163, PD-1 and MHC-I, all these markers being more frequently expressed on the former group compared to the latter. Conclusion: The tumour immune microenvironment of pre-therapy TURB lesions of patients achieving a complete or major patho- logic response after neoadjuvant pembrolizumab shows significant enrichment for T cells and myeloid cells, for stromal or tumour PD-L1 as well as increased MHC-I expression on tumour cells compared to lesions from non responders. Funding: Grant support. Ministry of Health, Lombardy and Tuscany regions, Bando Ricerca Finalizzata, grant number NET-2016-02361632 OFP-05-011 CD163+ M2 macrophage tissue infiltration and urinary soluble CD163 in IgA nephropathy V. Agrawal*, S. Singh, S. Kamthan, N. Prasad, V. Agarwal *SGPGIMS, India Background & objectives: Macrophages play an important role in renal inflammation and fibrosis. We evaluated M2 macrophage (CD163+) infiltration in IgAN and correlated it with other param- eters of monocyte activation including monocyte-derived circu- lating microparticles (MMPs), urinary soluble CD163 (sCD163), KIM-1 and MCP-1. Methods: Twenty-one IgAN, classified with Oxford MEST-C score, two age and sex-matched healthy and four Lupus Nephri- tis (LN) disease controls were included. Plasma MMPs (Annex- inV+/CD14+), quantified by flow cytometry were estimated as % of total MPs. CD163 immunohistochemistry (clone-EP324) was performed on renal biopsies and quantified in glomeruli and the tubulo-interstitium. Urinary sCD163, KIM-1 and MCP-1 levels were estimated by ELISA. S21