CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
乳腺癌中 CD47 与 CD68 表达与 TIL（肿瘤浸润淋巴细胞）、血管侵犯、检测方式及预后的关联
英文原题：CD47 and CD68 expression in breast cancer is associated with tumor-infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis.
查看英文原题
CD47 and CD68 expression in breast cancer is associated with tumor-infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis.
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中文摘要
肿瘤细胞表达的CD47与巨噬细胞上的信号调节蛋白α结合，启动对吞噬作用的抑制。我们研究了乳腺癌中CD47的肿瘤表达与CD68巨噬细胞含量、TIL（肿瘤浸润淋巴细胞）亚群以及血管侵犯之间的关系。
我们检查了来自挪威乳腺癌筛查计划的282例基于人群的系列病例（200例筛查检出和82例间期患者）。在组织微阵列（TMA）玻片上评估了CD47和CD68的免疫组化染色。对于CD47评估，使用了染色指数。对CD68肿瘤相关巨噬细胞进行计数并二分类。在TMA玻片上通过免疫组化对TIL亚群（CD45、CD3、CD4、CD8和FOXP3）进行计数并二分类。血管侵犯（淋巴管和血管）在全组织玻片上确定。高CD47肿瘤细胞表达或高CD68巨噬细胞计数与所有TIL亚群水平升高（p < 0.02）、CD163巨噬细胞（p < 0.001）、血管侵犯（CD31阳性）（p < 0.01）以及高肿瘤细胞Ki67（p < 0.004）显著相关。高CD47表达与ER阴性（p < 0.001）、HER2阳性状态（p = 0.03）和间期检出肿瘤（p = 0.03）相关。通过多因素分析，在校正肿瘤直径、组织学分级、淋巴结状态和分子亚型后，CD47-CD68联合高表达与较短的无复发生存期（RFS）相关（风险比[HR]：2.37，p = 0.018）。通过多因素评估，luminal A肿瘤患者在CD47-CD68高表达病例中显示较短的RFS（HR：5.73，p = 0.004）。
本研究表明，CD47肿瘤细胞高表达与CD68巨噬细胞高计数同时存在，与多种TIL亚群、血管侵犯（CD31阳性）、其他侵袭性肿瘤特征及间期乳腺癌相关。
我们的发现提示CD47、肿瘤免疫应答与血管侵犯（CD31阳性）之间存在关联。CD47-CD68联合高表达是所有病例以及luminal A亚型中与不良预后相关的独立预后因素。
展开英文摘要原文
CD47 expressed on tumor cells binds to signal regulatory protein alpha on macrophages, initiating inhibition of phagocytosis.
We investigated the relationships between tumor expression of CD47 and CD68 macrophage content, subsets of tumor-infiltrating lymphocytes (TILs), and vascular invasion in breast cancer. A population-based series of 282 cases (200 screen detected and 82 interval patients) from the Norwegian Breast Cancer Screening Program was examined. Immunohistochemical staining for CD47 and CD68 was evaluated on tissue microarray (TMA) slides. For CD47 evaluation, a staining index was used. CD68 tumor-associated macrophages were counted and dichotomized. TIL subsets (CD45, CD3, CD4, CD8, and FOXP3) were counted and dichotomized using immunohistochemistry on TMA slides. Vascular invasion (both lymphatic and blood vessel) was determined on whole tissue slides.
High CD47 tumor cell expression or high counts of CD68 macrophages were significantly associated with elevated levels of all TIL subsets (p < 0. 02), CD163 macrophages (p < 0. 001), blood vessel invasion (CD31 positive) (p < 0. 01), and high tumor cell Ki67 (p < 0. 004). High CD47 expression was associated with ER negativity (p < 0. 001), HER2 positive status (p = 0. 03), and interval-detected tumors (p = 0.
03). Combined high expression of CD47-CD68 was associated with a shorter recurrence-free survival (RFS) by multivariate analysis (hazard ratio [HR]: 2. 37, p = 0. 018), adjusting for tumor diameter, histologic grade, lymph node status, and molecular subtype. Patients with luminal A tumors showed a shorter RFS for CD47-CD68 high cases by multivariate assessment (HR: 5. 73, p = 0. 004).
This study demonstrates an association of concurrent high CD47 tumor cell expression and high CD68 macrophage counts with various TIL subsets, blood vessel invasion (CD31 positive), other aggressive tumor features, and interval-presenting breast cancer.
Our findings suggest a link between CD47, tumor immune response, and blood vessel invasion (CD31 positive). Combined high expression of CD47-CD68 was an independent prognostic factor associated with poor prognosis in all cases, as well as in the luminal A category.
论文信息
- 作者
- Chen Y、Klingen TA、Aas H、Wik E、Akslen LA
- 单位
- Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway.Norway
- 文献类型
- 非美国政府资助研究
- 期刊
- The journal of pathology. Clinical research2023 May
- 原文标识
- PubMed 36598153 · DOI 10.1002/cjp2.309
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