title: Hidden malignant cells within leukocyte aggregates: seeds for invasive and metastatic cancer?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taiwan.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Hsiao
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Mason
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: Yan-gao
authors.initials: YG
authors.lastname: Man
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology*; D009208:Myoepithelioma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009366:Neoplasm Seeding; D009367:Neoplasm Staging; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor