Immunohistochemical localization of the plasminogen activator inhibitor-1 in breast cancer.
We used an immunohistochemical assay with an antigen-retrieval technique to study plasminogen activator inhibitor type-1 (PAI-1) expression in paraffin-embedded breast tissue samples at different stages of malignant transformation. We detected PAI-1 in 15/20 invasive tumors. In several cases staining was localized to the stromal component. PAI-1-positive fibroblasts could be seen surrounding tumor nodules or at tumor margins. In addition, tumor-infiltrating macrophages (13 cases) and endothelial cells (5 cases) were positive. In 11 specimens PAI-1-positive cancer cells were also detected. In 2 strongly positive cases secreted PAI-1 was visible in the extracellular matrix surrounding the cells. Six of 9 samples of carcinoma in situ (DCIS) were weakly positive. No staining of endothelial cells was visible in DCIS. Only a few positive adenomatous epithelial cells could be seen in 3 of 7 papillomas. All biopsies of normal breast tissue were negative, with the exception of one sample, obtained from a patient with a previous segmental mastectomy for DCIS. PAI-1 production by invasive breast cancers could reflect a general upregulation of the plasminogen activation system in proliferating cancer cells, as suggested by the finding that normal mammary epithelium cultures expressed PAI-1 in all cases examined. In addition, production of PAI-1 by the tumor stroma could protect the tumor itself from excessive proteolysis.
Bianchi
E
E
Geraldine Brush Cancer Research Institute, California Pacific Medical Center, San Francisco 94115.
Cohen
R L
RL
Dai
A
A
Thor
A T
AT
Shuman
M A
MA
Smith
H S
HS
D001483:Base Sequence; D001940:Breast / Q000737:chemistry / Q000166:cytology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology; D002278:Carcinoma in Situ / Q000737:chemistry / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000737:chemistry; D005354:Fibrosarcoma / Q000737:chemistry / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic; D010212:Papilloma / Q000737:chemistry / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D010996:Pleural Effusion / Q000737:chemistry / Q000473:pathology; D013347:Subcellular Fractions / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator