The myofibroblast is the predominant plasminogen activator inhibitor-1-expressing cell type in human breast carcinomas.
The tumor level of plasminogen activator inhibitor-1 (PAI-1) is an informative biochemical marker of a poor prognosis in several cancer types. However, the tumor biological functions of PAI-1 and the identity of PAI-1-expressing cells are controversial. With the aim of immunohistochemically localizing PAI-1 in formalin-fixed, paraffin-embedded invasive ductal breast carcinoma samples, we raised new polyclonal antibodies against PAI-1 from different expression systems. The antibodies were affinity purified by absorption on immobilized preparations of PAI-1 different from those used for immunization. The specificity of the antibodies was ensured by immunoblotting analysis. In immunohistochemistry, the staining pattern obtained with the antibodies showed a good correlation with the PAI-1 mRNA expression pattern. In all 25 cases analyzed, PAI-1 immunoreactivity was predominantly localized in fibroblast-like cells. Double-immunofluorescence analyses showed co-expression of PAI-1 and alpha-smooth muscle actin in these cells, suggesting that they are myofibroblasts. PAI-1 was also seen in some myoepithelial cells surrounding occasional foci of ductal carcinoma in situ (9 of 25), some endothelial cells (8 of 25), some cancer cells (3 of 25), and some mast cells (6 of 25). In conclusion, we have provided a robust immunohistochemical procedure for detection of PAI-1 and shown that the majority of the PAI-1-expressing cells in invasive ductal breast carcinomas are myofibroblasts.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, Building 5, DK-8000 Aarhus C, Denmark. bvo@oncology.dk
Birgitte Vrou
BV
Offersen
Boye Schnack
BS
Nielsen
Gunilla
G
Høyer-Hansen
Fritz
F
Rank
Stephen
S
Hamilton-Dutoit
Jens
J
Overgaard
Peter A
PA
Andreasen
D000199:Actins / Q000378:metabolism; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000276:immunology
D000199:Actins; D000906:Antibodies; D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1