Chung Jae-Hoon, Lee Chung-Un, Lee Dong-Hyeon, Song Wan
Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Department of Urology, Ewha Womans University Medical Center, Ewha Womans University School of Medicine, Seoul 07985, Korea.
Biomedicines. 2022 Apr 15;10(4):910. doi: 10.3390/biomedicines10040910.
The expression and prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TICs) has not been determined in urothelial carcinoma (UC) with variant histology. We retrospectively reviewed 90 patients (44 with micropapillary variant of UC (MPUC) and 46 with UC with squamous differentiation (UCSD)) who underwent radical cystectomy between January 2013 and December 2019. The expression of PD-L1 in TICs was measured using the VENTANA (SP-142) immunohistochemistry assay and dichotomized using a 5% cutoff value (positive ≥ 5%). Kaplan-Meier survival analysis was used to estimate recurrence-free survival (RFS), and multivariable Cox proportional hazard models were used to identify factors predicting tumor recurrence. Overall, positive PD-L1 expression in TICs was confirmed in 50 of 90 (55.6%) patients (40.1% (18/44) of MPUC and 69.9% (32/46) of UCSD). RFS was significantly shorter in patients with positive PD-L1 expression in TICs than in those with negative PD-L1 expression both in MPUC ( = 0.005) and UCSD ( = 0.046). Positive PD-L1 expression in TICs was significantly associated with an increased risk of tumor recurrence in both MPUC (HR = 1.85; 95% CI: 1.323-2.672; = 0.017) and UCSD (HR = 1.58; 95% CI: 1.162-2.780; = 0.032). In conclusion, positive PD-L1 expression in TICs was significantly associated with poorer RFS in both MPUC and UCSD patients. Our results support the use of adjuvant immunotherapy in these patients if they test positive for PD-L1 in their TICs.
程序性死亡配体-1（PD-L1）在具有组织学变异的尿路上皮癌（UC）肿瘤浸润免疫细胞（TICs）中的表达及预后作用尚未明确。我们回顾性分析了2013年1月至2019年12月期间接受根治性膀胱切除术的90例患者（44例微乳头型UC（MPUC）和46例伴有鳞状分化的UC（UCSD））。采用VENTANA（SP-142）免疫组化检测法测定TICs中PD-L1的表达，并以5%的临界值进行二分法分类（阳性≥5%）。采用Kaplan-Meier生存分析评估无复发生存期（RFS），并使用多变量Cox比例风险模型确定预测肿瘤复发的因素。总体而言，90例患者中有50例（55.6%）TICs中PD-L1表达呈阳性（MPUC患者中为40.1%（18/44），UCSD患者中为69.9%（32/46））。在MPUC（P = 0.005）和UCSD（P = 0.046）中，TICs中PD-L1表达阳性的患者RFS均显著短于PD-L1表达阴性的患者。在MPUC（HR = 1.85；95%CI：1.323 - 2.672；P = 0.017）和UCSD（HR = 1.58；95%CI：1.162 - 2.780；P = 0.032）中，TICs中PD-L1表达阳性均与肿瘤复发风险增加显著相关。总之，在MPUC和UCSD患者中，TICs中PD-L1表达阳性均与较差的RFS显著相关。我们的结果支持对这些TICs中PD-L1检测呈阳性的患者使用辅助免疫疗法。
