Abstract 5402: Urothelial carcinomas in different anatomical positions exhibit distinct genomic and immunological characteristics

Abstract

Abstract Background Human bladder cancers were recently suggested to be grouped into different molecular subtypes. However, little is known about the difference in gene landscape between upper tract urothelial carcinoma (UTUC) and lower tract urothelial carcinoma (LTUC) of Chinese patients. Herein, we analyzed the genomic characteristics of primary UTUC and LTUC in China. Methods The formalin-fixed paraffin-embedded specimens of 250 LTUC and 121 UTUC patients have been consecutively collected and have underwent next-generation sequencing (NGS) from 2018 to 2021 in 3DMed Clinical Laboratory Inc. Gene mutation and TMB level were analyzed by NGS, detected PD-L1 expression by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Results NGS analysis showed that, in the samples of UTUC, the top ten gene mutations were CDKN2A/2B 6.6% (8/121), TP53 5.8% (7/121), FGF19 5.8% (7/121), TERT 3.3% (4/121), PREX2 3.3% (4/121), FRS2 3.3% (4/121), KDM6A 2.5% (3/121), PIK3CA 2.5% (3/121), EGFR 2.5% (3/121), MYCL 2.5% (3/121); while in the LTUC, the top gene mutations were TP53 44.4% (111/250), TERT 31.6% (79/250), CDKN2A/2B 25.7% (64/250), FGF3 18% (45/250), KDM6A 17.6% (44/250), PIK3CA 16.4% (41/250), RB1 14.0%(35/250), DGFR3 13.6% (34/250), ARID1A 12.4% (31/250). Furthermore, TMB level and PD-L1 expression in the UTUC and LTUC were also analyzed, and results showed that although the gene mutation was totally different, but no significant difference was found on TMB level (p>0.05). However, among these patients, higher PD-L1 expression level were found in UTUC than LTUC (p<0.05). Conclusion UTUC and LTUC in Chinese patients hold different gene landscape and PD-L1 expression, this suggested these patients may have different prognosis and response differently to targetable therapy and immunotherapy. Citation Format: Ruiqian Li, Hushan Zhang, Qilin Wang, Hong Yang, Yu Bai, Chen Hu, Hongyi Wu, Chongjian Zhang, Ziyong Wang, Qiwei Wang, Pengjie Xu, Jun Li. Urothelial carcinomas in different anatomical positions exhibit distinct genomic and immunological characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5402.