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根据既定评分标准评估的程序性死亡受体1配体(PD-L1)表达在恶性唾液腺肿瘤中的预后影响:肿瘤比例评分(TPS)、联合阳性评分(CPS)和免疫细胞(IC)浸润

Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate.

作者信息

Witte Hanno M, Gebauer Niklas, Lappöhn Daniela, Umathum Vincent G, Riecke Armin, Arndt Annette, Steinestel Konrad

机构信息

Institute of Pathology and Molecular Pathology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany.

Department of Haematology and Oncology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany.

出版信息

Cancers (Basel). 2020 Apr 3;12(4):873. doi: 10.3390/cancers12040873.

Abstract

BACKGROUND

Malignant neoplasms of the salivary glands are rare, and therapeutic options are limited. Results from recently published studies indicate a possible use for checkpoint inhibition in a subset of patients, but there are no established criteria for programme cell death ligand 1 (PD-L1) scoring in salivary gland carcinomas (SGCs).

METHODS

In this retrospective study, we present a cohort of 94 SGC patients with full clinical follow-up. We included 41 adenoid cystic carcinomas (AdCC), 21 mucoepidermoid carcinomas (MEC), 16 acinic cell carcinomas (ACC), 12 adenocarcinomas, not otherwise specified (AC, NOS), 2 epithelial-myoepithelial carcinomas (EMC), one salivary duct carcinoma (SDC), and one carcinoma ex pleomorphic adenoma (CA ex PA). Subsequent histopathological analysis was performed with special emphasis on the composition of the immune cell infiltrate (B-/T-lymphocytes). We assessed PD-L1 (SP263) on full slides by established scoring criteria: tumor proportion score (TPS), combined positivity score (CPS) and immune cell (IC) score.

RESULTS

We identified significantly elevated CD3+, TP, CP, and IC scores in AC, NOS compared to AdCC, MEC, and ACC. CPS correlated with node-positive disease. Moreover, AC, NOS displayed IC scores of 2 or 3 in the majority (67%) of cases (p = 0.0031), and was associated with poor prognosis regarding progression-free (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001). CPS correlated with strong nuclear or null p53 staining in AC, NOS but not in other SGCs. Long-lasting partial remission could be achieved in one AC, NOS patient who received Pembrolizumab as third-line therapy.

CONCLUSIONS

The current study is the first to investigate the use of established scoring criteria for PD-L1 expression in malignant salivary gland tumors. Our findings identify unique characteristics for AC, NOS among the family of SGCs, as it is associated with poor prognosis and might represent a valuable target for immune checkpoint inhibition.

摘要

背景

涎腺恶性肿瘤较为罕见,治疗选择有限。最近发表的研究结果表明,检查点抑制在一部分患者中可能有用,但涎腺癌(SGC)中程序性细胞死亡配体1(PD-L1)评分尚无既定标准。

方法

在这项回顾性研究中,我们纳入了94例接受全面临床随访的SGC患者。其中包括41例腺样囊性癌(AdCC)、21例黏液表皮样癌(MEC)、16例腺泡细胞癌(ACC)、12例未另行规定的腺癌(AC,NOS)、2例上皮-肌上皮癌(EMC)、1例涎腺导管癌(SDC)和1例多形性腺瘤癌变(CA ex PA)。随后进行组织病理学分析,特别关注免疫细胞浸润(B/T淋巴细胞)的组成。我们根据既定的评分标准在全切片上评估PD-L1(SP263):肿瘤比例评分(TPS)、联合阳性评分(CPS)和免疫细胞(IC)评分。

结果

我们发现,与AdCC、MEC和ACC相比,AC,NOS中的CD3 +、TP、CP和IC评分显著升高。CPS与淋巴结阳性疾病相关。此外,AC,NOS在大多数(67%)病例中显示IC评分为2或3(p = 0.0031),并且与无进展生存期(PFS)(p < 0.0001)和总生存期(OS)(p < 0.0001)的不良预后相关。CPS与AC,NOS中强烈的核p53染色或无p53染色相关,但在其他SGC中不相关。一名接受派姆单抗作为三线治疗的AC,NOS患者实现了长期部分缓解。

结论

本研究首次探讨了在恶性涎腺肿瘤中使用既定评分标准评估PD-L1表达。我们的研究结果确定了AC,NOS在SGC家族中的独特特征,因为它与不良预后相关,可能是免疫检查点抑制的一个有价值的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7801/7226358/d1e1e9f57009/cancers-12-00873-g001.jpg

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