ECP 2023 Abstracts

S14 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 *University Medical Center Schleswig-Holstein, Campus Kiel, Depart- ment of Pathology, Kiel, Germany Background & objectives: Fibroblast activation protein (FAP) expressed by cancer-associated fibroblasts can be targeted in thera- nostics in various solid tumours. We investigated the immunohisto- chemical expression of FAP in stroma and tumour cells of pancreatic neuroendocrine tumours (PanNETs) in relation to hormone expression. Methods: 31 PanNETs were analysed. Histological and immunohisto- chemical (synaptophysin, chromogranin A, Ki67, islet hormones, SSTR2) classification was conducted. Semiquantitative analysis of hormone expres- sion was performed. Percentage of FAP expression and staining intensity was measured semiquantitatively in tumour and stroma cells and confirmed using digital image analysis (QuPath). FAP expression was correlated with hormone expression and clinicopathological characteristics. Results: 27 (87 %) of PanNETs showed hormone expression (26 % insulin, 48 % glucagon, 58 % PP, 13 % somatostatin, 13 % gastrin, 10 % serotonin). 84 % of PanNETs showed membranous positivity (2+ or 3+) for SSTR2. Membranous and cytoplasmatic FAP expression in tumour cells was observed in 45 % of PanNETs. All FAP-positive PanNETs expressed glucagon. FAP was detected in stroma fibroblast in 87 % of PanNETs (39 % positivity in 1 % - 10 % of stromal cells; 19 % positivity in 11 % - 50 % of stromal cells; 29 % positivity in > 50 % of stromal cells in PanNETs), including SSTR2-negative tumours. Conclusion: Membranous FAP expression was observed in cancer- associated fibroblasts in the stroma of PanNETs with varying inten- sity. Moreover, tumour cells of glucagon-positive PanNETs displayed cytoplasmatic positivity. Targeting FAP broadens imaging options and therefore could be a promising approach in glucagon-positive PanNETs as well as in insulin-positive, SSTR2-negative PanNETs. Funding: Franziska Kellers participates in the Clinician Scientist Program in Evolutionary Medicine (CSEM) at University Medi- cal Center Schleswig-Holstein supported by the DFG (Deutsche Forschungsgemeinschaft). OFP-04 | Joint Oral Free Paper Session Uropathology / Nephropathology OFP-04-001 For those who like to see numbers in pathology reports when his- tological grading is blurry... E.D. Serbes*, M.C. Karaburun, K. Obaid, M. Babayigit, M.C. Gogus, S. Baltaci, E. Suer, S. Kiremitci, D. Enneli *Ankara University Medicine School, Pathology Department, Turkey Background & objectives: In this study, we aimed to investigate the prognostic significance of the ratio of accompanying low-grade areas in high-grade non-muscle invasive bladder carcinomas (NMIBC), which are at the intermediate/high-risk group and received intravesical BCG therapy. Methods: A preliminary cohort of 148 patients diagnosed as high- grade NMIBC at transurethral resection (TUR) specimens and com- pleted at least one cycle of induction and maintenance BCG therapy at our institution between 2010-2020 was included. The percentage of low-grade areas of the tumour was determined in the initial TUR specimens of every case. Clinical follow-up information (recurrence/ progression, survival data) were obtained. Results: While 70% (104/148) of the tumours had pure high- grade morphology(group-1), 30% had low-grade component ranging from 5 to 80%(group-2). The median follow-up time of the group-1 and 2 were 32 and 35 months, respectively. The pro- gression rate in the group-1(10,5%) was significantly higher than group-2 (4,54%)(p=0.033), whereas no such significant difference was found regarding recurrence rate (p=0.098). Within group-2, 23/44 cases <=20% low-grade areas (group-2a) and 21/44 cases had >20% (group-2b). There was no statistical difference between group-2a and group-2b regarding recurrence rates, but progression rate was higher in the group-2a (p=0.019). Kaplan-Meier survival analysis, univariate/multivariate regression analysis were planned to be done after the evaluation of the whole cohort. Conclusion: According to the latest World Health Organization (WHO) classification, urothelial carcinomas with 5% high-grade his- tology are considered as high-grade. However, high-grade NMIBCs containing 0% and 95% low-grade components are tumours located at two different ends in terms of the low-grade component ratio and our preliminary study revealed that the risk of progression rate significantly increases when low grade areas were limited in a percentage of 20% in the initial TUR specimens of high-grade NMIBC. OFP-04-002 Molecular subtyping of upper urinary tract urothelial carcinomas with surrogate immunohistochemical markers E.D. Serbes*, M. Babayigit, S. Sevim, E. Suer, M.C. Gogus, S. Kiremitci, D. Enneli *Ankara University Medicine School, Pathology Department, Turkey Background & objectives: Studies on molecular subtyping of upper urinary tract urothelial carcinomas (UTUC) are limited, which is a dis- tinct entity from urinary bladder carcinomas (UBC). We aimed to per- form basal/luminal phenotyping of UTUCs by using surrogate immu- nohistochemical markers and to investigate its prognostic significance. Methods: Fifty patients diagnosed with UTUC on radical nephro- ureterectomy specimens at our institution between 2009-2019 were included in the study. Tumours were all high grade conventional urothelial carcinomas. Those with any concomitant/previous diagnosis of UBC were excluded. An antibody panel of CK5/6, CD44, CK20, p53 was applied immunohistochemically, to identify basal/luminal molecu- lar subtypes and investigate their prognostic role in UTUCs. Results: The mean follow-up time of the patients (mean age:67,range:37-81) was 42.6 months (±21.4). 18/50 (36%) patients showed intravesical recurrence after a mean follow-up period of 7.94 months. Twenty-six cases (52%) died, of which 20(76.9%) were cancer- related. Twenty-five(50%), 19(38%), 4(8%) cases showed basal-like, luminal-like and mixed(basal and luminal-like) immunophenotypes, respectively, 2(4%) cases showed null-phenotype. Univariate-Cox- analysis of disease-free survival (DFS) revealed that CD44(hazard- ratio:0.14, p=0.004) or CK5/6(hazard-ratio:0.108, p=0.001) expres- sion indicating basal-like phenotype were favourable prognostic factors, whereas CK20(hazard-ratio:26.159,p=0.001) and p53(hazard- ratio:4.394,p=0.004) expression were poor prognostic factors. Signifi- cantly higher intravesical recurrence was observed in CK5/6-negative UTUCs (p=0.035), despite of no correlation with other markers. In multivariate-cox-analysis of DFS, CK20-positivity in UTUCs indicated 9.5 times increased risk (p=0.047) and basal-like immunophenotype indicated better prognosis (p=0.006). Conclusion: In the present study, we investigated the prognostic role of basal/luminal immunophenotyping and p53 expression in UTUCs. CK20 and p53 expression indicated poor prognosis, whereas basal-like phenotype correlated with significantly more favourable prognosis, in contrary to its poor prognostic effect in UBC. CK5/6 negativity was found to be correlated with a significantly increased risk of intravesi- cal recurrence. Although these results look promising in predicting prognosis and risk of intravesical recurrence in UTUCs, they need to be confirmed by further studies. OFP-04-003 Does GATA3 expression contribute to diagnosis in renal tumours with eosinophilic/oncocytic features? C. Utku*, B. Sarsik Kumbaraci, B. Yaman, M.S. Kalemci, S. Sen *Department of Pathology, Ege University Faculty of Medicine, Izmir, Turkey