Localization of mRNA for bone morphogenetic protein-6 in skeletal metastases from prostate cancer and other common human malignancies by in situ hybridization

Introduction: Osteoblastic skeletal metastases are common in prostate cancer and lead to significant morbidity. Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo. We have reported that mRNA for BMPs is expressed in primary prostate cancer, with differential expression favouring BMP-6 as a potential marker and possible mediator of skeletal metastases. We have also shown that mRNA for BMP-6 is exclusively expressed in epithelial malignant cells of the prostate, predominantly in primary tumours with established metastatic secondaries. The aim of this study was to investigate BMP-6 expression in skeletal metastases from prostatic adenocarcinoma, as well as in other common human malignancies, by in situ hybridization (ISH). Patients and methods: Twenty patients with skeletal metastases from different primary cancers were investigated, including prostate (three), lung (eight), kidney (two), breast (five), colon (one) and uterus (one). Metastatic tissue was formalin-fixed, paraffin-embedded and decalcified. RNA probes were generated from the human BMP-6 cDNA and ISH was performed using a non-isotopic method. Results: mRNA for BMP-6 was identified in normal osteoblasts and used as an internal positive control. The strongest positive signals were detected in skeletal prostatic cell deposits (two of three metastases) and weaker signals were present in five other metastatic deposits from primary lung (one of eight), breast (three of five) and colon (one of one) cancers. Conclusions: BMP-6 mRNA is strongly expressed in prostatic adenocarcinoma, in the primary tumour as well as in bone metastases, and is also expressed, although less frequently, in skeletal secondaries from other human malignancies. Our findings suggest that BMP-6 may have potential as an attractive marker of skeletal metastases, particularly in prostate cancer. Its possible role in the pathogenesis of osteoblastic metastases requires further investigation and clarification.