BMP-2 Protein Expression in Clear Cell Renal Carcinoma

Introduction. Bone morphogenetic protein-2 (BMP-2) is a member of BMP family of proteins. In human, it has role in skeletal repair and regeneration, as well as in heart formation. Kidneys of BMP-2 heterozygous null mutant mice have normal gross anatomy, but exhibit increased ureteric bud branching. Dysregulation of BMP-2 signaling has been suggested in carcinogenesis. Methods. We determined BMP-2 protein expression in CCRC and in healthy renal tissue, and evaluated its prognostic significance after five years of follow-up. Twenty patients with localized clear cell carcinomas at the time of diagnosis were included in the investigation. Immunohistochemical staining for BMP-2 was evaluated semiquantitatively and the specimens were scored according to the distribution of positive cells. Results. In normal tissue, the expression of BMP-2 was localized predominantly in tubular cells, with less intensive staining in glomerular mesangial cells. Other glomerular cells were BMP-2 negative. The cellular staining pattern for BMP-2 was both cytoplasmic and membranous. In 14 of 20 patients, loss of BMP-2 staining was observed in the malignant tissue. However, three out of six patients with positive BMP-2 staining died from disseminated malignant disease, one of them had concomitant acute myeloid leukemia. Conclusions. According to our results, BMP-2 expression in CCRC may be associated with an adverse outcome with development of bone metastatic disease.