Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
Breast Cancer Res Treat. 2018 Feb;167(3):649-658. doi: 10.1007/s10549-017-4558-0. Epub 2017 Nov 1.
While the role of natural killer (NK) cells in breast cancer therapy has been investigated, little information is known about NK cell function and presence in nonmalignant and premalignant breast tissue. Here, we investigate and quantify NK cell marker CD56 and activating ligand MICA in breast tissue with benign breast disease.
Serial tissue sections from 88 subjects, 44 with benign breast disease (BBD) who remained cancer-free, and 44 with BBD who later developed cancer, were stained with H&E, anti-MICA, and anti-CD56. Up to ten representative lobules were identified on each section. Using digital image analysis, MICA and CD56 densities were determined for each lobule, reported as percent of pixels in the lobule that registered as stained by each antibody. Analyses were performed on a per-subject and per-lobule basis.
Per-subject multivariate analyses showed associations of CD56 and MICA with age: CD56 was increased in older subjects (p = 0.03), while MICA was increased in younger subjects (p = 0.005). Per-lobule analyses showed that CD56 and MICA levels were both decreased in lobules with fibrocystic change, with median levels of CD56 and MICA staining, respectively, at 0.31 and 7.0% in fibrocystic lobules compared to 0.76 and 12.2% in lobules without fibrocystic change (p < 0.001 for each). Among fibrocystic lobules, proliferative/atypical lobules showed significantly lower expression compared to nonproliferative lobules for MICA (p = 0.02) but not for CD56 (p = 0.80).
Levels of CD56+ NK cells and activating ligand MICA were decreased in breast lobules with fibrocystic change, and MICA levels showed a significant stepwise decrease with increasing histopathologic abnormality. MICA levels were also significantly decreased in older subjects, who generally have higher risk of developing cancer. These findings advance a model in which MICA promotes cytotoxic activity in CD56+ NK cells to protect against tumorigenesis in breast lobules, and suggest further research is warranted.
虽然自然杀伤 (NK) 细胞在乳腺癌治疗中的作用已经得到研究，但关于 NK 细胞在非恶性和癌前乳腺组织中的功能和存在知之甚少。在这里，我们研究并量化了良性乳腺疾病中 NK 细胞标志物 CD56 和激活配体 MICA。
对 88 名受试者的连续组织切片进行了研究，其中 44 名受试者患有良性乳腺疾病 (BBD) 且无癌症，44 名受试者患有 BBD 且后来发展为癌症。对这些切片用 H&E、抗-MICA 和抗-CD56 进行染色。在每个切片上最多识别十个有代表性的小叶。使用数字图像分析，确定每个小叶的 MICA 和 CD56 密度，报告为每个抗体染色的小叶像素的百分比。分析是在每个受试者和每个小叶的基础上进行的。
多变量受试者分析显示 CD56 和 MICA 与年龄相关：CD56 在年龄较大的受试者中增加（p=0.03），而 MICA 在年龄较小的受试者中增加（p=0.005）。小叶分析显示，CD56 和 MICA 水平在伴有纤维囊性改变的小叶中均降低，纤维囊性小叶中 CD56 和 MICA 染色的中位数水平分别为 0.31%和 7.0%，而无纤维囊性改变的小叶中分别为 0.76%和 12.2%（p<0.001 ）。在纤维囊性小叶中，与非增生性小叶相比，增生性/非典型小叶的 MICA 表达显著降低（p=0.02），而 CD56 表达则没有差异（p=0.80）。
在伴有纤维囊性改变的乳腺小叶中，CD56+NK 细胞和激活配体 MICA 的水平降低，MICA 水平随着组织病理学异常程度的增加而呈显著逐步下降。MICA 水平在年龄较大的受试者中也显著降低，而年龄较大的受试者通常有更高的患癌风险。这些发现提出了一个模型，即 MICA 促进 CD56+NK 细胞的细胞毒性活性，以保护乳腺小叶免受肿瘤发生，并表明需要进一步研究。
Zotero 插件
