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(American Journal of Pathology. 2003;163:1887-1899.)
© 2003 American Society for Investigative Pathology

The Myofibroblast Is the Predominant Plasminogen Activator Inhibitor-1-Expressing Cell Type in Human Breast Carcinomas

Birgitte Vrou Offersen^*, Boye Schnack Nielsen, Gunilla Høyer-Hansen, Fritz Rank, Stephen Hamilton-Dutoit, Jens Overgaard^* and Peter A. Andreasen^¶

From the Department of Experimental Clinical Oncology^*and the Institute of Pathology,Aarhus University Hospital, Aarhus; the Department of Molecular Biology,^¶Aarhus University, Aarhus; the Finsen Laboratory,Copenhagen; and the Department of Pathology,Copenhagen University Hospital, Copenhagen, Denmark

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 -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.

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