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程序性死亡配体-1 和肿瘤浸润淋巴细胞在 HER2 基因过表达的乳腺癌中的作用。

The role of programmed death ligand-1 and tumor-infiltrating lymphocytes in breast cancer overexpressing HER2 gene.

机构信息

Department of Pathology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY, 14263, USA.

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

出版信息

Breast Cancer Res Treat. 2018 Jul;170(2):293-302. doi: 10.1007/s10549-018-4745-7. Epub 2018 Mar 9.


DOI:10.1007/s10549-018-4745-7
PMID:29524062
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6002907/
Abstract

PURPOSE: The purpose of the study is to investigate the prognostic significance of programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2+ breast cancer (BC). METHODS: HER2+ BC cases (n  = 191) were collected between 1996 and 2013. Tissue microarray (TMA) slides were stained with two clones of PD-L1 antibodies (28-8 and 22C3) and the percentage of positive membranous staining was scored. TILs of the full sections were also scored using percentage scale. RESULTS: Clone 28-8 had expression in ≥ 1% of the tumor cells in 25.7% of the cases, while clone 22C3 in ≥ 1% of the tumor cells was expressed in 11.5% of the cases. In the multivariate analysis, higher expression of PD-L1 (clone 28-8) in tumor correlated with lower risk of tumor recurrence, with HR of 0.4 (p = 0.033). Higher level of TILs (> 15%) predicts better overall survival (OS) in all patients with HR of 0.35 (p  = 0.0046). In the group of patients who were treated with trastuzumab-based adjuvant chemotherapy, lower PD-L1 (clone 28-8) expression in TILs correlated with tumor recurrence (p  = 0.034). In the group of patients who were treated with non-trastuzumab-based adjuvant chemotherapy, lower TILs and lower PD-L1 (clone 28-8) expression in tumor had borderline statistical significance in association with tumor recurrence (p  = 0.064 and 0.083, respectively). In the group of patients who were treated with trastuzumab-based adjuvant chemotherapy, PD-L1 or TILs was not statistically significant to predict 5-year survival. In the group of patients who were treated with non-trastuzumab-based adjuvant chemotherapy, low TILs (p = 0.009) correlated with 5-year death due to disease. CONCLUSION: We conclude that PD-L1 may have prognostic significance in HER2+ BCs.

摘要

目的:本研究旨在探讨程序性死亡配体 1(PD-L1)表达和肿瘤浸润淋巴细胞(TIL)在人表皮生长因子受体 2(HER2)阳性乳腺癌(BC)中的预后意义。

方法:收集了 1996 年至 2013 年间的 HER2+BC 病例(n=191)。使用两种 PD-L1 抗体(28-8 和 22C3)对组织微阵列(TMA)切片进行染色,并对阳性膜染色的百分比进行评分。还使用百分比量表对全切片的 TIL 进行评分。

结果:在 25.7%的病例中,克隆 28-8 在≥1%的肿瘤细胞中表达,而在 11.5%的病例中克隆 22C3 在≥1%的肿瘤细胞中表达。在多变量分析中,肿瘤中 PD-L1(克隆 28-8)的高表达与肿瘤复发风险降低相关,风险比(HR)为 0.4(p=0.033)。在所有患者中,TIL 水平较高(>15%)预示着更好的总生存(OS),HR 为 0.35(p=0.0046)。在接受曲妥珠单抗为基础的辅助化疗的患者中,TIL 中较低的 PD-L1(克隆 28-8)表达与肿瘤复发相关(p=0.034)。在接受非曲妥珠单抗为基础的辅助化疗的患者中,TIL 较低和肿瘤中 PD-L1(克隆 28-8)表达较低与肿瘤复发具有统计学意义(p=0.064 和 0.083)。在接受曲妥珠单抗为基础的辅助化疗的患者中,PD-L1 或 TIL 对预测 5 年生存率无统计学意义。在接受非曲妥珠单抗为基础的辅助化疗的患者中,TIL 较低(p=0.009)与 5 年疾病死亡相关。

结论:我们得出结论,PD-L1 可能在 HER2+BCs 中具有预后意义。

相似文献

[1]
The role of programmed death ligand-1 and tumor-infiltrating lymphocytes in breast cancer overexpressing HER2 gene.

Breast Cancer Res Treat. 2018-3-9

[2]
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[6]
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[3]
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[5]
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[6]
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[7]
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[8]
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[9]
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本文引用的文献

[1]
Assessment of Concordance between 22C3 and SP142 Immunohistochemistry Assays regarding PD-L1 Expression in Non-Small Cell Lung Cancer.

Sci Rep. 2017-12-5

[2]
Interplay between Natural Killer Cells and Anti-HER2 Antibodies: Perspectives for Breast Cancer Immunotherapy.

Front Immunol. 2017-11-13

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Prognostic Significance of Stromal Versus Intratumoral Infiltrating Lymphocytes in Different Subtypes of Breast Cancer Treated With Cytotoxic Neoadjuvant Chemotherapy.

Appl Immunohistochem Mol Morphol. 2018-9

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Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study.

Lancet Oncol. 2017-1

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Immune checkpoints in aggressive breast cancer subtypes.

Neoplasma. 2016

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Programmed Cell Death Ligand-1 Blockade in Urothelial Bladder Cancer: To Select or Not to Select.

J Clin Oncol. 2016-9-10

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The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers.

Oncoimmunology. 2015-8-31

[8]
Targeting PD-1/PD-L1 in the treatment of metastatic renal cell carcinoma.

Ther Adv Urol. 2015-12

[9]
Companion diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC.

Expert Rev Mol Diagn. 2016

[10]
Prognostic significance of PD-L1 and PD-L2 in breast cancer.

Hum Pathol. 2016-1

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