Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma

Abstract

The importance of neoangiogenesis for the progressive growth and viability of solid tumors is well established. Recently, there has been growing evidence that angiogenesis might also be important in hematological malignancies, but only few data are available. In this report, we have studied the impact of bone marrow microvessel density and survival in patients with multiple myeloma (MM). Immunohistochemical CD34 stained paraffin-embedded bone marrow biopsies of 44 patients with newly diagnosed MM were studied. Microvessels were counted in 400 x magnification and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). The median MVD was 48 vessels/mm2, the range was 0-125 vessels/mm2. Using a cut-off value of the median MVD in the Kaplan-Meier analysis, the median survival was 22.2 months in the group with the higher MVD and was not reached in the group with the lower MVD (P< 0.01). In a multivariate Cox regression analysis, using previously identified prognostic factors beta2-microglobulin, C-reactive protein (CRP), and age, MVD remained significant as a prognostic factor (P< 0.03).

Prognostic value of bone marrow angiogenesis in multiple myeloma: Use of light microscopy as well as computerized image analyzer in the assessment of microvessel density and total vascular area in multiple myeloma and its correlation with various clinical, histological, and laboratory parameters

“…Similar to our experience Sezar et al [20] found a significant difference in the survival of patients with low-and high-grade bone marrow microvessel density. They found that in a multivariate Cox proportional hazards model, using previously identified prognostic factors, i.e., b 2 microglobulin, C-relative protein, and age, MVD remained a significant prognostic factor.…”

“…Few studies of angiogenesis in multiple myeloma have been done [11][12][13][14][15][16][17][18][19][20][21]. All the studies done in the literature for angiogenesis in MM measured microvessel density (MVD) in the ''hot spots.''…”

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

“…These enzymes are involved in the degradation of the basement membrane and the extracellular matrix, and promote the migration and proliferation of endothelial cells to form a new blood vessel (Moses, 1997;Zetter, 1998). In human MM, VEGF and bFGF are secreted by tumour cells and the concentrations of these angiogenic factors are higher in more advanced disease (Vacca et al, 1998;Bellamy et al, 1999;Dankbar et al, 2000;Di Raimondo et al, 2000;Sezer et al, 2000;. MM cells also secrete MMPs (Barillé et al, 1997(Barillé et al, , 1999Vanderkerken et al, 2000) and uPA (Hjertner et al, 2000) and their conditioned medium is able to stimulate the proliferation and migration of endothelial cells (Vacca et al, 1998(Vacca et al, , 1999.…”

“…The human U266 MM cell line and bone marrow plasma cells from patients with active MM display a strong angiogenic potential (Vacca et al, 1998(Vacca et al, , 1999Laroche et al, 2001). Moreover, bone marrow MVD also seems to be a prognostic factor of survival in MM patients (Sezer et al, 2000).…”

Tumor Angiogenesis Is Associated with Plasma Levels of Stromal-Derived Factor-1α in Patients with Multiple Myeloma

“…Sections (3 Am) of mercuric chloride -fixed paraffinembedded biopsy specimens were obtained from the posterior iliac crest of multiple myeloma and MGUS patients and healthy agematched subjects. The sections were immunostained using a monoclonal antibody against CD34, as previously described (2,6). The MVD for each biopsy was determined by counting the number of individually stained microvessels (capillaries and small venules not exceeding 10 Am) at Â200 magnification in three areas of highest vessel density according to the accredited ''hotspot'' method, as previously described (17).…”