Institute of Medicine, Chung Shan Medical University, Taiwan.
Cancer Epidemiol. 2011 Oct;35(5):475-9. doi: 10.1016/j.canep.2010.11.010. Epub 2011 Feb 2.
Our previous studies revealed that leukocyte infiltration into aged or injured myoepithelial cell layers is a key trigger for breast tumor invasion and metastasis. Our current study further assessed the possibility that leukocyte aggregates may harbor detached individual tumor cell or clusters of tumor cells.
Tissue sections from patients with pregnancy-associated breast cancer (PABC) and controls were subjected to morphological and immunohistochemical assessment with a panel of leukocyte and tumor cell related markers.
A total of 63 leukocyte aggregates were detected in the 20 PABC cases studied. Of these, 55 (87%) were distributed within normal or hyperplastic lobules adjacent to invasive lesions. Over 70% of these leukocyte aggregates harbored detached individual tumor cell or cell clusters with malignant properties, including strong p53 positivity, elevated proliferation, reduced cell surface adhesion molecules, and cytological resemblance to adjacent invasive cancer cells. A significant number of these tumor cells or condensed chromosomes of mitotic tumor cells were observed to conjoin with the plasma membrane of leukocytes. Similar alterations were seen in leukocyte aggregates within the inter-lobular space and in non-PABC with a lower frequency.
These findings suggest that leukocyte infiltration may trigger dissemination of tumor cells from their primary site, and that leukocyte aggregates may serve as a reservoir for disseminated tumor cells that may be physically dragged to distant sites by leukocytes during their migration.
我们之前的研究表明，白细胞浸润到衰老或受伤的肌上皮细胞层是乳腺肿瘤侵袭和转移的关键触发因素。我们目前的研究进一步评估了白细胞聚集物中是否可能存在分离的单个肿瘤细胞或肿瘤细胞簇。
对来自妊娠相关性乳腺癌（PABC）患者和对照者的组织切片进行形态学和免疫组织化学评估，使用一组与白细胞和肿瘤细胞相关的标志物。
在研究的 20 例 PABC 病例中，共检测到 63 个白细胞聚集物。其中，55 个（87%）分布在邻近侵袭性病变的正常或增生小叶内。超过 70%的白细胞聚集物中含有分离的单个肿瘤细胞或具有恶性特征的肿瘤细胞簇，包括强 p53 阳性、增殖增加、细胞表面黏附分子减少以及与邻近侵袭性癌细胞的细胞学相似性。观察到大量这些肿瘤细胞或有丝分裂肿瘤细胞的浓缩染色体与白细胞的质膜相连。在小叶间空间的白细胞聚集物和非 PABC 中也观察到类似的改变，但频率较低。
这些发现表明，白细胞浸润可能触发肿瘤细胞从原发部位扩散，白细胞聚集物可能是播散性肿瘤细胞的储存库，在白细胞迁移过程中，这些肿瘤细胞可能会被白细胞物理性地拖到远处。
