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膀胱癌根治性切除术患者的生存结局与微卫星不稳定性、肿瘤浸润淋巴细胞和程序性死亡配体-1 表达的关系。

Relationship between survival outcomes and microsatellite instability, tumor infiltrating lymphocytes and programmed cell death ligand-1 expression in patients with bladder cancer and radical cystectomy.

机构信息

Medical Oncology, Bakirkoy Sadi Konuk Training and Research Hospital, Istanbul, Turkey.

出版信息

J BUON. 2021 Sep-Oct;26(5):2117-2125.

Abstract

PURPOSE

Platin-based chemotherapies are first-line treatment methods after surgery in bladder cancer. Recently, novel immunotherapies emerged after platin-based regimens. The purpose of this study was to evaluate the prognostic significance of microsatellite instability (MSI), tumor infiltrating lymphocytes (TILs) and programmed cell death ligand-1 (PD-L1) expression which are used as predictive biomarkers in immunotherapy.

METHODS

Clinical and pathological features of bladder cancer patients who underwent radical cystectomy were retrospectively analyzed from their records in this single-center study. PD-L1, PD-L1 on TIL, PMS2, MSH2, MSH6 and MLH1 immunohistochemistry staining were carried out to archieve resected tumor specimens of the eligible patients. MSI was evaluated according to existing of PMS2, MSH2, MSH6 and MLH1.

RESULTS

MSI was high in 24.6% of 61 patients. PD-L1 expression on tumor cells and PD-L1 expression on TIL were positive in 14.8% and 16.4% of the patients, respectively. Intratumoral TIL rate was >10% in 12 patients (19.7%). There was no statistically significant relationship between PD-L1, PD-L1 on TIL, MSI and TIL rate and patients' characteristics including sex, stage, pathologic grade and lymph node status. There was a positive trend between MSI-high patients and overall survival (OS) (p=0.089). Univariate analysis did not reveal any significant difference at 3-years OS with PD-L1 tumor expression and PD-L1 expression on TIL and TIL rate >10% (p=0.822, p=0.638, p=0.318, respectively) Conclusion: This study revealed that there is a positive trend between OS and MSI but no prognostic significance of PD-L1 and TIL which are proven predictive biomarkers of immunotherapy in patients with bladder cancer.

摘要

目的

铂类化疗是膀胱癌手术后的一线治疗方法。最近,在铂类方案之后出现了新的免疫疗法。本研究旨在评估微卫星不稳定性(MSI)、肿瘤浸润淋巴细胞(TILs)和程序性死亡配体-1(PD-L1)表达作为免疫治疗预测生物标志物的预后意义。

方法

本单中心研究回顾性分析了接受根治性膀胱切除术的膀胱癌患者的临床和病理特征。对合格患者的切除肿瘤标本进行 PD-L1、TIL 上的 PD-L1、PMS2、MSH2、MSH6 和 MLH1 免疫组织化学染色,以评估 MSI 根据 PMS2、MSH2、MSH6 和 MLH1 的存在情况进行评估。

结果

61 例患者中有 24.6%为 MSI 高。肿瘤细胞上的 PD-L1 表达和 TIL 上的 PD-L1 表达阳性率分别为 14.8%和 16.4%。12 例患者(19.7%)肿瘤内 TIL 率>10%。PD-L1、TIL 上的 PD-L1、MSI 和 TIL 率与患者的性别、分期、病理分级和淋巴结状态等特征之间无统计学显著关系。MSI 高患者与总生存(OS)呈正相关(p=0.089)。单因素分析显示,PD-L1 肿瘤表达、TIL 上的 PD-L1 表达和 TIL 率>10%与 3 年 OS 无显著差异(p=0.822、p=0.638、p=0.318)。

结论

本研究表明,OS 与 MSI 呈正相关,但膀胱癌患者中已被证明是免疫治疗预测生物标志物的 PD-L1 和 TIL 无预后意义。

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