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根据既往化疗和免疫治疗情况,首次复发的高级别和低级别复发腔面型、基底型和双阴性P53突变型非肌层浸润性膀胱癌的无复发生存率和PD-L1表达情况

Relapse-Free Survival and PD-L1 Expression in First High- and Low-Grade Relapsed Luminal, Basal and Double-Negative P53-Mutant Non-Muscular Invasive Bladder Cancer Depending on Previous Chemo- and Immunotherapy.

作者信息

Blinova Ekaterina, Enikeev Dmitry, Roshchin Dmitry, Samyshina Elena, Deryabina Olga, Tertychnyy Aleksander, Blinov Dmitry, Kogan Evgenia, Dudina Marina, Barakat Haydar, Merinov Dmitrij, Kachmazov Aleksandr, Serebrianyi Stanislav, Potoldykova Natalia, Perepechin Dmitrij

机构信息

Department of Clinical Anatomy and Operative Surgery, Department of Pathological Anatomy, Institute for Urology and Reproductive Health, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, Russia.

Department of Oncological Urology, Russian National Research Center of Radiology, 3 2nd Botkinsky Proezd, 125284 Moscow, Russia.

出版信息

Cancers (Basel). 2020 May 21;12(5):1316. doi: 10.3390/cancers12051316.

Abstract

The goal of this study was to assess how PD-L1 expression in tissue specimens of patients with main molecular subtypes of NMIBC (luminal, basal and double-negative p53-mutant) associates with relapsed-free survival in dependence on the tumor grade and prior treatment of primary bladder cancer. PD-L1 expressions on the membrane of neoplastic and CD8+ immune cells were assessed in tumor specimens ( = 240) of primary and relapsed luminal, basal and double-negative p53-mutant NMIBC. Association between relapse-free survival and PD-L1 expression was estimated for high- and low-grade relapsed NMIBC according to previous treatment and their molecular profile, using the Kaplan-Meier method, and assessed by using the log-rank test. Potential confounders were adjusted by Cox regression models. In a group of patients who underwent only TUR without intravesical therapy, there were significant differences in relapse time between high- and low-grade tumors in basal and luminal molecular subtypes; for basal relapsed carcinoma, RFS was shorter in cases where tumors were less malignant. Both intravesical mitomycin and Bacillus Calmette-Guerin (BCG) therapy significantly extended the time of recurrence of low-grade luminal and basal bladder malignancies with no intergroup differences in double-negative NMIBC. PD-L1 expression status was associated with RFS for luminal relapsed NMIBCs in the group without previous frontline intervention, and with RFS in the group of patients with luminal relapsed bladder cancer previously utilized BCG. Obtained results may be considered as a promising approach for further clinical implementation.

摘要

本研究的目的是评估非肌层浸润性膀胱癌(NMIBC)主要分子亚型(腔面型、基底型和p53突变双阴性型)患者组织标本中的程序性死亡配体1(PD-L1)表达如何根据肿瘤分级和原发性膀胱癌的既往治疗情况与无复发生存相关。在原发性和复发性腔面型、基底型和p53突变双阴性型NMIBC的肿瘤标本(n = 240)中评估肿瘤细胞和CD8 +免疫细胞表面的PD-L1表达。根据既往治疗及其分子特征,采用Kaplan-Meier法估计高级别和低级别复发性NMIBC的无复发生存与PD-L1表达之间的关联,并使用对数秩检验进行评估。通过Cox回归模型调整潜在混杂因素。在仅接受经尿道膀胱肿瘤切除术(TUR)而未进行膀胱内治疗的一组患者中,基底型和腔面型分子亚型的高级别和低级别肿瘤在复发时间上存在显著差异;对于基底型复发性癌,肿瘤恶性程度较低的病例无复发生存期较短。膀胱内丝裂霉素和卡介苗(BCG)治疗均显著延长了低级别腔面型和基底型膀胱恶性肿瘤的复发时间,双阴性NMIBC组间无差异。在未进行过一线干预的组中,PD-L1表达状态与腔面型复发性NMIBC的无复发生存相关,在先前使用过BCG的腔面型复发性膀胱癌患者组中也与无复发生存相关。所获结果可被视为进一步临床应用的一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6830/7281187/d870d0da0327/cancers-12-01316-g0A1a.jpg

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