Alterations of microvascular density in bone metastases of adenocarcinomas

Bone may provide an extremely fertile microenvironment for angiogenesis. Experimental investigations indicate angiogenesis as a major regulator of bone metastasis development. Vascularization and angiogenic potential is known for most of the primary tumor types, but no studies investigated angiogenesis in bone metastases of human cancers. We have evaluated microvessel density of bone metastases of various cancer types (all adenocarcinomas) and compared to their primary tumors in paraffin samples of 39 patients. Microvessel density was determined by using the hot spot method and the blood vessel marker, CD34. The most vascularized adenocarcinoma was found to be renal cell cancer followed by lung adenocarcinoma, while breast cancer was heterogenous in this respect. Two patterns of modulation of the angiogenic phenotype in the bone metastases emerged in this study, which seemed to be cancer type specific: decreased angiogenic potential characterizing 45% of renal cell cancers and breast cancers of high vascularity in their primary, and increased angiogenic potential characterizing 40% of lung adenocarcinomas and breast cancers of low vascularity in their primary lesion. Our data demonstrate that i., the vascularization of bone metastases is frequently altered compared to the primary tumors, ii., patterns are different in the case of various cancer types. The tumor-type specific alterations of the angiogenic phenotype of cancers, metastatic to the bone, can have a clinical significance when angiosuppressive therapies are considered.