UROKINASE RECEPTOR LOCALIZATION IN BREAST-CANCER AND BENIGN LESIONS ASSESSED BY IN-SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRY

The serine protease urokinase-type plasminogen activator (uPA) mediate s cancer invasion and metastasis by binding to a cell surface receptor (uPA-R, CD87) on both tumor and stromal cells. In the present study w e assessed uPA-R distribution in formalin-fixed, paraffin-embedded bre ast cancer specimens (n=50) and benign lesions (n=10) by immunohistoch emistry employing a newly developed polyclonal chicken antibody to uPA -R (pAb HU277) in parallel with established monoclonal antibody (mAb) 3936 to uPA-R. In addition, uPA-R mRNA synthesis was investigated by i n situ hybridization. In all of the sections analyzed, macrophage-like cells reacted with either antibody type. In 22 of the 50 cancer speci mens, tumor cells reacted with pAb HU277 in contrast to mAb 3936 which only stained 9 of the 22 positive cases. Nevertheless, in 49 of the 5 0 cases, uPA-R mRNA was detected in cancer and in stromal cells by in situ hybridization suggesting posttranscriptional regulation of uPA-R expression in breast cancer cells. In 18 of 50 cases, uPA-R mRNA was a lso visualized in blood vessel lining endothelial cells by in situ hyb ridization and applying pAb HU277 in 14 of these 18 cases by immunohis tochemistry. mAb 3936 did not stain any endothelial cells. pAb HU277 r eacted with the breast gland epithelial cells of benign lesions as wel l, in contrast to mAb 3936 which did not. As for the cancer tissue, in benign lesions, endothelial cells were sporadically stained by pAb HU 277. This antibody, but not mAb 3936, also stained myoepithelial cells in intraductal areas of invasive breast carcinoma. The results presen ted demonstrate the usefulness of pAb HU277 in locating uPA-R in tu mo r and normal cells with high sensitivity in formalin-fixed, paraffin-e mbedded breast tissue.