The differential expression of the
ras oncogene product p21 in the primary
tumor, regional nodes, and distant metastatic sites in patients with disseminated
breast cancer was examined to define the
biologic and clinical significance of the ras oncogene in the progression of
breast cancer. The
avidin-
biotin peroxidase complex method was used on
formalin-fixed,
paraffin-embedded tissues from 16 patients with metastatic disease. The primary antibody used in this protocol was RAP-5, an anti-p21 murine monoclonal
IgG2a. p21
antigen staining was similar in the primary
tumor and regional nodes from the same patient (P less than 0.05), but the staining of distant
metastases was more variable. Expression of ras p21 was consistently increased in invasive components of the primary
tumor as compared with intraductal
tumor. In addition, a high level of p21 expression was seen in
tumor emboli in lymphatics and blood vessels as compared with contiguous
tumor in parenchymal tissue. Although p21 staining is present in aggressive primary breast
cancers and most metastatic sites, our findings indicate that markedly enhanced p21 expression is associated with the earlier stages (invasion and dissemination) of aggressive breast
cancers.