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评估化生型乳腺癌中的免疫密度、PD-L1 和 CXCR4 表达,以预测潜在的免疫治疗获益。

Evaluation of immune density, PD-L1, and CXCR4 expressions in metaplastic breast carcinoma to predict potential immunotherapy benefit.

机构信息

Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Millet Caddesi, Çapa, Fatih, 34390, Istanbul, Turkey.

Department of Surgical Oncology Unit, Institute of Oncology, Istanbul University, Istanbul, Turkey.

出版信息

Med Oncol. 2023 Dec 15;41(1):18. doi: 10.1007/s12032-023-02243-y.

DOI:10.1007/s12032-023-02243-y
PMID:38102446
Abstract

Metaplastic breast carcinoma (MBC) -rare but fatal subtype of invasive breast carcinomas- provides limited benefit from conventional triple-negative breast carcinoma chemotherapy. We aimed to determine the immune density of this tumor and to evaluate of programmed death-ligand 1 (PD-L1) and chemokine receptor type 4 (CXCR4) expressions to determine whether it would benefit from immunotherapy. Clinicopathological characteristics of 85 patients diagnosed as MBC between 1997 and 2017 were retrospectively assessed. We evaluated the immunohistochemical expression of PD-L1 and CXCR4, and the extent of tumour infiltrating lymphocytes (TILs), with survival data. TILs groups were statistically significantly associated with lymph node status, histological subtype, squamous component, local recurrence and/or systemic metastasis, and disease-related deaths (p < 0.05). PD-L1 positivity in immune cells (ICs) has a statistically significant relationship with the presence of squamous component (p = 0.011) and HER2 positivity (p = 0.031). PD-L1 positivity in tumor cells (TCs) was found to be significantly more frequent in high-TILs density (p = 0.003). PD-L1 combined positive score was significantly associated with the tumors containing high-TILs density (p = 0.012) and squamous component (p = 0.035). Disease-free and disease-specific survival rates were found to be longer for the cases displaying PD-L1 positivity in ICs; and also PD-L1 positivity in ICs was found to be an independent prognostic factor. When the expression of CXCR4 was compared with clinicopathological and survival parameters, no statistically significant association was found (p > 0.05). Based on the results of this retrospective study, PD-L1 and TILs appear to be prognostic. This study provides rationale for further studies to determine whether a subset of patients with metaplastic breast cancer could derive a meaningful benefit from immune-targeting therapies.

摘要

化生性乳腺癌(MBC)——一种罕见但致命的浸润性乳腺癌亚型——从常规三阴性乳腺癌化疗中获益有限。我们旨在确定这种肿瘤的免疫密度,并评估程序性死亡配体 1(PD-L1)和趋化因子受体 4(CXCR4)的表达,以确定其是否受益于免疫治疗。回顾性评估了 1997 年至 2017 年间诊断为 MBC 的 85 例患者的临床病理特征。我们评估了 PD-L1 和 CXCR4 的免疫组织化学表达以及肿瘤浸润淋巴细胞(TIL)的程度,并结合生存数据进行分析。TIL 组与淋巴结状态、组织学亚型、鳞状成分、局部复发和/或全身转移以及疾病相关死亡有统计学显著相关性(p<0.05)。免疫细胞(IC)中 PD-L1 阳性与存在鳞状成分(p=0.011)和 HER2 阳性(p=0.031)有统计学显著关系。高 TIL 密度组中肿瘤细胞(TC)中 PD-L1 阳性的频率明显更高(p=0.003)。PD-L1 联合阳性评分与含有高 TIL 密度的肿瘤(p=0.012)和鳞状成分(p=0.035)显著相关。显示 IC 中 PD-L1 阳性的病例无复发生存率和疾病特异性生存率较长;IC 中 PD-L1 阳性也是独立的预后因素。当比较 CXCR4 的表达与临床病理和生存参数时,未发现统计学显著相关性(p>0.05)。基于这项回顾性研究的结果,PD-L1 和 TIL 似乎具有预后意义。这项研究为进一步研究确定是否可以从免疫靶向治疗中获益提供了依据。

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