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VISTA和PD-L1在肾上腺皮质癌中的表达及临床意义

Expression and clinical significance of VISTA and PD-L1 in adrenocortical carcinoma.

作者信息

Zhang Ziwei, Li Menglian, Wang Jianjun, Liu Mengsi, Chen Huan, Lou Yuan, Wang Yijie, Sun Qi, Zhu Dalong, Li Ping, Bi Yan

机构信息

Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

出版信息

Endocr Relat Cancer. 2022 May 27;29(7):403-413. doi: 10.1530/ERC-22-0066.

Abstract

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and challenging management. The present study aimed to investigate the expression of programmed death ligand-1 (PD-L1) and V-domain Ig-containing suppressor of T cell activation (VISTA) in ACC and their associations with clinicopathological features and survival outcomes. Immunohistochemistry was performed on formalin-fixed paraffin-embedded specimens from 54 ACC patients. Chi-square/Fisher's exact tests or independent samples t/Mann-Whitney U tests were performed to assess correlations between immunoscores and clinicopathological parameters. The Kaplan-Meier method and Cox regression were conducted for survival analysis and to identify independent predictors of overall (OS) and disease-free (DFS) survival. Results showed that VISTA was expressed in tumor cells (TCs) and tumor-infiltrating immune cells (TICs) in 81.5% (44/54) and 40.7% (22/54) of the patients, respectively. PD-L1 positivity was found in either TCs or TICs in 11.1% (6/54) of the patients. Patients with positive VISTA expression in TCs had a higher tumor stage (56.9% vs 20%, P = 0.036) and Ki-67 index (30.50 ± 23.51% vs 14.76 ± 11.75%, P = 0.006). However, PD-L1 positivity in either TCs or TICs had no association with patient clinicopathological features. A higher VISTA expression intensity, a larger area and a higher immunoscore were associated with increased risks of disease progression and overall mortality, but PD-L1 expression in TCs or TICs was not associated with OS or DFS. In conclusion, positive TC VISTA expression was correlated with pathological parameters related to malignancy in ACC patients. This finding provides novel evidence of the value of VISTA, in addition to PD-L1, as an immunotherapeutic target in ACC.

摘要

肾上腺皮质癌(ACC)是一种罕见的恶性肿瘤,预后较差,治疗具有挑战性。本研究旨在探讨程序性死亡配体1(PD-L1)和含V结构域免疫球蛋白的T细胞激活抑制因子(VISTA)在ACC中的表达及其与临床病理特征和生存结果的关系。对54例ACC患者的福尔马林固定石蜡包埋标本进行免疫组织化学检测。采用卡方检验/费舍尔精确检验或独立样本t检验/曼-惠特尼U检验来评估免疫评分与临床病理参数之间的相关性。采用Kaplan-Meier法和Cox回归进行生存分析,并确定总生存期(OS)和无病生存期(DFS)的独立预测因素。结果显示,分别有81.5%(44/54)和40.7%(22/5

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