Immunolocalization of bone morphogenetic protein-6 in benign and malignant prostatic tissue: Correlation with in situ hybridization
Autzen P., Horne CHW., Steward M., Henry L., McIntosh G., Robinson MC., Robson CN., Neal DE., Hamdy FC.
Introduction: Bone morphogenetic proteins (BMPs) are able to induce ectopic bone formation in vivo. BMPs are known to be expressed in benign and malignant prostatic tissue, and preliminary studies have shown BMP-6 to be expressed only in advanced prostate cancer. The aims of this study were (i) to localize BMP-6 protein in benign and malignant prostatic tissue using a novel anti-human BMP-6 antibody, and (ii) to correlate immunolocalization of BMP-6 with mRNA expression investigated by in situ hybridization (ISH). Patients and methods: Of 39 men investigated. 29 had metastatic disease and 11 had BPH. Tissue samples were formalin-fixed and paraffin-embedded. Immunohistochemistry (IHC) was carried out using a monoclonal mouse anti-human antibody (Novocastra Laboratories, UK). For ISH. RNA probes were generated from the human BMP-6 cDNA. Results: mRNA was located in the cytoplasm of the malignant epithelial cells. The protein was mainly localized to the cytoplasm of epithelial cells, but in three cases the staining was nuclear. Nineteen of 20 patients were positive for BMP-6 by ISH and 1 5 of the 20 were positive by IHC. In the localized cancers, two of 11 showed positive signals by ISH and seven of the 11 were positive by IHC. None of the BPH cases showed any evidence of BMP-6 expression by ISH, but four of the eight cases were positive by IHC. The positive staining in BPH was associated with histological evidence of inflammatory changes. Conclusions: BMP-6 mRNA and protein are located only within the prostatic epithelial cells. Whereas mRNA was exclusively expressed in prostate cancers, the protein was detected in both benign and malignant cells. BMP-6 gene and protein expression appear to be associated with the presence of skeletal metastases in prostate cancer. To our knowledge, this is the first BMP-6 immunolocalization study using an antihuman monoclonal antibody. Further studies are warranted to assess the potential value of BMP-6 immunostaining in prostate cancer. © 1997 British Journal of Urology.