ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 of PBRM1 is significantly correlated with PD-L1 expression in ccRCC. This result can suggest that the PD-L1 blockade may not be effective even though the PD-L1 was expressed in ccRCC due to the interference of PBRM1 alteration. Funding: This research was funded by the Seoul National University Bundang Hospital Research Fund (grant number: 02-2018-015). PS-26-040 Comparison of urinary cytology reported using the Paris Sys- tem with follow-up biopsies: a single institutional experience Y.K. Akgök*, G. Gümrükçü, M. Doğan, S. Kılar Kösemen *Haydarpasa Numune Education and Research Hospital, Turkey Background & objectives: The Paris System (TPS) provided stand- ardized cytomorphological criteria and terminology for the recognition of high-grade urothelial malignancies. The aim of this study was to evaluate the role of The Paris System by comparing urinary cytology with follow-up biopsies. Methods: Urinary cytologies with follow-up biopsy up to 3 months from 2017 to 2021 were evaluated with TPS. The atypical urothe- lial cells category was also evaluated as positive. Inadequate uri- nary cytologies and samples submitted for decoy cell examination were excluded. Statistical analyses were performed by calculat- ing sensitivity, specificity, positive and negative predictive value, diagnostic accuracy, and risk of high-grade malignancy (ROHM). Results: A total of 203 samples were evaluated. 82.3% of the cases were categorized as negative, 7.4% AUC, 1.5% suspicious for high- grade urothelial carcinoma (SHGUC) and 8.9% high-grade urothelial carcinoma (HGUC). ROHM was 6.0% for the negative category, 40.0% for AUC, 100.0% for SHGUC, and 100.0% for HGUC. In the reporting of urinary cytology, the sensitivity of TPS was 72.0%, the specific- ity was 94.6%, the positive predictive value was 75.0%, the negative predictive value was 93.6%, and the diagnostic accuracy was 90.6%. Conclusion: TPS has high specificity and negative predictive value for detecting high grade urothelial lesions. We found that ROHM increases gradually from negative category to HGUC. And we think that TPS has an important role in the detecting of high-grade lesions and reporting urinary cytology. PS-26-041 Molecular characterization of the neuroendocrine variant of urothelial bladder carcinoma R. Abou-Jaoudé*, J. Fontugne, N. Sirab, V. Dixon, C. Krucker, F. Radvanyi, Y. Allory *Institut Curie, France Background & objectives: Diagnosis of neuroendocrine (NE) bladder carcinoma (BC) remains challenging. Our aim was to compare consen- sus molecular subtyping and new immunohistochemical markers in a series of cases with morphology suggesting NE differentiation. Methods: BC tumours with morphology suggesting NE differen- tiation were identified and stained using multiplex IHC (subtype markers CK5/6-GATA3), Ki67 and NE IHC markers (Chromogra- nin A, Synaptophysin, INSM1, TUBB2B). In tumours with adja- cent non-NE morphology, the IHC expression of each area was individually assessed. Transcriptomic profiling was performed using 3’RNA-seq to determine consensus molecular subtype, including multiple samples in heterogeneous cases. Results: We included 14 patients (9 men and 5 women) with a median age of 75 years. Ten cases were associated with area(s) of non-NE morphology. Twenty-eight samples from 14 patients underwent 3’RNA- seq. Applying the consensus classifier, 9/14 cases (64.3%) had at least one neuroendocrine-like subtype area. Of the 6/9 NE-like cases with multiple sequenced areas, 4 harboured distinct subtypes (Basal/Squamous, Luminal Unstable and/ or Stroma-rich). NE-like tumours were characterized by negative or focal/weak CK5/6-GATA3 immunophenotype (quickscore <0.1 in 7/9). Six of 9 NE-like tumours showed INSM1 positivity, while non-NE-like tumours were all INSM1 negative. Further analysis of the other NE markers and their respective performance to identify NE-like subtype is ongoing. Conclusion: Neuroendocrine bladder carcinoma is associated with intratumoral heterogeneity at the mor phological, immunohistochemical and molecular levels. Preliminary results show that the majority of NE-like molecular subtype tumours are characterized by CK5/6-GATA3 double negative phenotype. Further analysis to determine the performance of NE markers (chromogranin A, synaptophysin, TUBB2B and INSM1) in identifying the aggressive NE-like consensus molecular subtype is ongoing. PS-26-042 Alpha-methylacyl-CoA racemase in carcinoma in situ of the urinary bladder: a useful addition or not C. Weinans*, A. zur Hausen, V. Winnepenninckxs, B. Vanneste, E. Speel, G. Roemen, T. Marcelissen, J. van Roermund, X. Li, K. Smits, I. Samarska *Department of Pathology, Maastricht University Medical Cen- tre+, Maastricht, The Netherlands Background & objectives: Diagnosing carcinoma in situ (CIS) of urothelium may be challenging. CK20, p53 and Ki-67 are common immunohistochemical markers to differentiate CIS from reactive epi- thelial changes (REC). The value of AMACR is debatable. We evalu- ated AMACR immunoreactivity in CIS and REC. Methods: Twenty-two CIS and 33 REC cases from our institu- tion were included. All specimens were stained for previously mentioned IHC. Immunoreactivity for CK20, Ki-67 and AMACR was assessed as negative (≤1/3 of urothelial thickness) or posi- tive (>1/3). AMACR was additionally quantified as <5% or ≥5% expression of the urothelium. P53 was evaluated as wild-type or aberrant-type. Results: CK20 was positive in all 22 CIS and in 8/33 REC cases, in accordance with the highest sensitivity of 100% and a specificity of 75.8%. In 10/22 CIS and in 6/33 REC cases p53 showed an aberrant pattern (sensitivity: 45.5%, specificity: 81.8%). Ki-67 was positive in 22 CIS and in 6 REC cases (sen- sitivity: 90.9%, specificity: 81.8%). The first scoring method showed that AMACR was positive in 16/22 CIS and negative in REC cases, leading to a sensitivity of 72.7% and the high- est specificity of 100%. Seventeen of 22 CIS and 2 REC cases showed AMACR expression in ≥5% of the urothelium (sensitiv- ity: 77.3%, specificity: 93.9%). Conclusion: According to these results the biomarker panel of CK20, Ki-67, AMACR and p53 appears to be useful for diagnoses of CIS in challenging cases giving the sensitivity and specificity. Also both scoring criteria for AMACR showed good correlation and similar sensitivity and specificity com- pared to each other and to the other IHC markers. Further study is necessary to evaluate the pitfalls and utility of AMACR in different settings. S179