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.
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.
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。
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