DNA错配修复
免疫疗法
生物标志物
医学
肿瘤科
微卫星不稳定性
膀胱癌
人口
癌症研究
免疫检查点
组织微阵列
内科学
林奇综合征
癌症
生物
基因
结直肠癌
遗传学
等位基因
微卫星
环境卫生
作者
Yuting Ma,Fang Hua,Xiu-Ming Zhong,Ying-Jie Xue,J. Li,Yanli Nie,Xuedong Zhang,Jan Ma,Cun-Hu Lin,Hao-Zhuang Zhang,Wenwu He,Dan Sha,Mingqiu Zhao,Zhigang Yao
标识
DOI:10.3389/fimmu.2023.1269097
摘要
Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.
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