Bone niorphogenetic protein-6 expression in radical prostatectomy specimens: Correlation with stage and progression
Johnson MI., Autzen P., Hoedemaaker R., Ruijter E., Neal DE., Robson CN., Hamdy FC.
Introduction: Skeletal metastases are predominantly osteoblastlc in prostate cancer; there is no explanation for this phenomenon. Bone niorphogenetic protein (BMP) refers to an activity derived from bone that induces ectopic bone formation in vivo. Pilot work showed differential expression of BMPs in prostatic tissue, with BMP-6 expressed in most primary tumours with bony secondaries. More recently, BMP-6 expression was investigated in primary prostate cancer and skeletal metastases, showing the presence of BMP-6 mRNA exclusively in malignant prostatic epithelial cells, both gene and protein in primary cancers with established skeletal métastases, as well as in secondary deposits, and infrequent expression in organ-confined disease. The aim of this study was to investigate the clinical significance of BMP-6 expression in patients with clinically localized prostate cancer undergoing radical prostatectomy. Patients and methods: Forty-six patients were investigated; all had clinically localized prostate cancer and underwent radical retropubic prostatectomy. The median follow-up was 7 years; 17 patients showed signs of disease progression. Tissue was formalin-fixed and paraffin-embedded; a monoclonal mouse anti-human antibody against BMP-6 was used for immunohistochemical staining. Results: BMP-6 was localized mainly to the cytoplasm of malignant epithelial cells; 33 patients showed positive staining for BMP-6. All 17 patients with evidence of disease progression were BMP-6 positive. Sixteen of 29 patients who had not progressed were also BMP-6 positive, including all 12 patients with extracapsular disease (six of whom had also lymph node métastases). Of the 17 patients with pathologically localized cancers, only four were BMP-6 positive. Conclusions: BMP-6 expression appears to correlate with stage and disease progression in clinically localized prostate cancer, and may be of use as a novel prognostic marker. Although the protein may not be specific to prostate cancer, its possible role in mediating metastatic and osteoblastic activity in prostate cancer requires further investigation. © 1998 British Journal of Urology.