ECP 2023 Abstracts

S16 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Results: In pts treated with VEGFR-TKI monotherapy, a significant correlation with PFS was observed with loss of PBRM1 expression (p=0.035), PD-L1 negativity (p=0.048), and high CD4/CD8 ratio (p=0.073). CD31 expression did not significantly correlate with PFS. A profile potentially predictive of angiogenesis (AP+) was defined based on the PBRM1 loss, PD-L1 negative, and high CD4/CD8. In pts treated with VEGFR-TKI monotherapy, tumours with the AP+ had a significantly longer median PFS (p=0.003) and mOS (p=0.024) compared to the oth- ers. The AP+ retained its significant correlation with PFS (p<0.001) and OS (p=0.006) in pts receiving VEGFR-TKI-based therapies. Conclusion: The AP+ signature (loss of PBRM1, PD-L1 negative, and CD4/CD8 highratio) was associated with improved clinical outcomes in mRCC pts at IMDC intermediate prognosis treated with VEGFR-TKI- based therapy; this correlation was significant regardless from the addition of IO to VEGFR-TKI monotherapy. Prospective validation of this signature is required for guiding the selection of the most appropriate 1L therapy. OFP-04-007 Basal phenotype is a peculiar feature of urothelial bladder carci- noma of young adults: a cohort analysis M. Valeri*, M. Iuzzolino, M. Cieri, L. Dore, A. Bressan, F. De Napoli, C. De Carlo, C. Rebecchini, L.M. Terracciano, P. Colombo *Humanitas University, Department of Biomedical Science, Pieve Emanuele, Milan, Department of Pathology, ASST Bergamo Est, Bolognini Hospital, Seriate, Bergamo, Italy Background & objectives: Urothelial carcinoma (UC) in young adults (YA, 18-40 years) is an uncommon, poorly understood and challenging disease for the clinical impact of potential recurrence and progression. Here we investigated the molecular phenotype and the genomic profile of a YAUC cohort. Methods: All YAUCs diagnosed in our department between 1998 and 2021 were reviewed. As surrogate of molecular subtyping, we employed immunohistochemical markers (CD44, CK5/6, CK20, GATA3) and a score system to stratify into Luminal and Basal pheno- type. Additionally, expression of Androgen receptor (AR) and RB1 was evaluated. In a subset of cases, NGS analysis was performed to search for genomic alterations. Results: Of the 51 cases collected, median age was 35 years and 42 patients were male; tumour grading was as follow: 36 low-grade (LG), 5 high-grade (HG), and 10 low malignant potential (PUNLMP) or papilloma (UP). All but 2 cases were pTa. Basal phenotype was the most common finding (44/51; 86,3%), with 43 cases both CK5/6+ and CD44+. Three HGUC were Luminal. AR and RB1 were expressed in 26 and 48 cases, irrespective of grading. NGS analysis of 10 cases showed FGFR2 mutation in 40% of tumours, while mutations in HRAS, KRAS, PIK3CA, CDKN2A, p53 were uncommon. Phenotype did not correlate with recurrence, possibly due to the limited number of events. Conclusion: The recent classification in molecular phenotypes and genomic alterations are still poorly investigated in YAUC. Our cohort showed a clear Basal phenotype and retention of RB1, although our data may be biased by the predominance of LGUC. In contrast to pre- vious published data, GATA3 did not act as a Luminal marker since all cases were positive. These results should be validated on a larger cohort of YAUC with a deeper investigation of molecular events related to this challenging category. OFP-04-008 Expanding the spectrum of eosinophilic solid and cystic renal cell carcinoma: molecular characterisation of borderline neoplasms from 25 patients reveals frequent alterations of TSC1, TSC2, and MTOR S. Williamson*, J. Van Arnam, K. Al-Obaidy, R. Humble, C. Kao, L. Schwartz, M. Tretiakova, T. Antic, L. Cheng, N. Gupta, J. McKenney, J. Nguyen, C. Przybycin, R. Alaghehbandan, S. Mohanty *Cleveland Clinic, USA Background & objectives: Eosinophilic solid and cystic (ESC) renal cell carcinoma (RCC) is accepted as a distinct renal neoplasm, with eosinophilic cell morphology, frequent keratin 20 positivity, and TSC1 / TSC2 gene alterations. We studied tumours with overlapping morphology for immunohistochemistry and genetics. Methods: We selected tumours (n=25) with partial features of ESC RCC: voluminous eosinophilic cells, solid architecture, keratin 20 positivity, cytoplasmic stippling, or hobnail-shaped cells, combined with atypical features, including papillary/tubular architecture, clear cells, foamy macrophages, psammoma bodies, end-stage renal disease (ESRD), concurrent papillary RCC, strong AMACR, or negative kera- tin 20. A next generation sequencing cancer gene panel was performed on 19. Results: Patients were 15:10 F:M, 48 to 76y. Unusual findings included ESRD (6) or multiple tumours (7 papillary/ESC-like). Only 3 were originally diagnosed as ESC. Keratin 20 most often was rare positive, 1-5% of cells. Five were negative and 3 showed higher per- centages of cells positive. Sequencing revealed alterations of TSC1 , TSC2 , or MTOR in 11 of 19, and one additional PIK3CA mutation. Eleven were reclassified as ESC or likely ESC. Seven were indeter- minate, either suggestive morphology/negative genetics or positive genetics/atypical morphology. One in an ESRD patient had KMT2C mutation (reported in ACKD RCC, although morphology was not clas- sic). Three were considered other entities: unclassified, papillary, and clear cell RCC. Conclusion: A substantial fraction of tumours with eosinophilic cells showing overlapping features of ESC RCC and papillary RCC are likely best classified as true ESC RCC, often with only rare keratin 20 positive cells. However, keratin 20 positivity can also be found in occasional non-ESC tumours. The morphologic spectrum of ESC is probably broader than previously thought, as only 3 of the most convincing 11 ESC tumours were originally diagnosed as such. OFP-04-009 Immune cell infiltration, tumour budding, and the p53 expression pattern are important predictors in penile squamous cell carci- noma: a retrospective study of 152 cases J. Hrudka*, Z. Prouzová, M. Kendall Bártů, J. Hojný, D. Čapka, N. Zavillová, R. Matej, P. Waldauf *UH Kralovske Vinohrady, Czech Republic Background & objectives: Penile squamous cell carcinoma is a rare malignancy with a slowly increasing incidence and variable prognosis. Regional lymph node involvement signifies poor prognosis but repre- sents a late sign, and more prognostic markers for effective patient risk stratification are urgently needed. Methods: 152 tumour samples were analysed for traditional pathologi- cal variables; tumour budding, p53, and p16 immunohistochemistry. The density of tumour lymphocytic infiltrate was subjectively deter- mined by two pathologists (brisk/non-brisk/absent) and also using the immunoscore method, which categorized the cohort into five groups according to the number of CD3+ and CD8+ T-cells in both the tumour centre and tumour invasion front. Results: Tumour budding count ≥ 5 tumour buds/20x power field and non-brisk/absent lymphocytic infiltrate were significant negative predic- tors of both the overall survival(OS) and cancer-specific survival(CSS), whereas a low immunoscore was a significant marker of shorter OS but not CSS. Advanced pT stage (3+4) was a significant marker of shorter CSS but not OS. In the multivariate analysis, high-grade budding was a significant parameter if adjusted for the patient`s age and associated variables, except for the pN stage. The lymphocytic infiltrate retained its prognostic significance if adjusted for age and associated variables. The negative prognostic significance of lymphatic, venous, and perineural invasion, lymph node metastasis, and p53 mutated profile was confirmed.