Neuropilin‐1 is differentially expressed in myoepithelial cells and vascular smooth muscle cells in preneoplastic and neoplastic human breast: A possible marker for the progression of breast cancer

Abstract

The expression and distribution of neuropilin‐1 (NRP‐1) was examined in the samples of normal human breast tissues and in non‐neoplastic and neoplastic areas of breast tissue removed for carcinoma using RT‐PCR as well as conventional and tissue microarrays immunohistochemical analyses. The NRP‐1 mRNA expression was significantly higher in neoplastic tissues as compared to normal breast samples. Immunohistochemically, the myoepithelial cells of the mammary ducts and lobules display positive reactions for NRP‐1, whereas the inner ductal and lobular epithelial cell layers failed to react. The myoepithelial cells of ducts and lobules in both neoplastic and non‐neoplastic tissue specimens displayed a stronger positive reaction for NRP‐1 than those in the normal breast. A positive reaction for NRP‐1, but with a gradual reduction in intensity, was observed in the myoepithelial cells of ducts with atypical epithelial hyperplasia and ductal carcinoma in situ (DCIS). The reaction was undetected or minimally detected in the areas of invasive carcinoma. NRP‐1 positive immunolabeling was also localized in the vascular smooth muscle cells and in some endothelial cells of the blood vessels in normal, non‐neoplastic and neoplastic breast tissue samples. In areas of breast carcinoma, NRP‐1 immunolabeling was more prominent in both vascular smooth muscle cells and in some endothelial cells than in similar cells in normal breast. The specificity of the newly developed antibody for NRP‐1 was confirmed by in situ hybridization with DIG‐labeled PCR generated probe. These results suggest that NRP‐1 may be a multiple function protein in human breast and may be involved in the induction of local invasiveness of neoplasia and angiogenesis and have direct relevance to the progression of breast cancer.