Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients

Abstract

Summary. We evaluated microvessel density (MVD) in bone marrow biopsies (BM) from multiple myeloma (MM) patients after staining with anti-CD34 and anti-CD105 antibodies (mAbs). The anti-CD105 mAb was significantly more sensitive than the anti-CD34 mAb in visualizing blood vessels both in controls and MM samples. MVD was significantly higher in MM than in controls with both anti-CD34 and anti-CD105 mAbs. Patients with low CD34 + MVD survived longer than patients with higher MVD (P = 0AE01), whereas there was no difference in survival between patients with low and high CD105 + MVD. Multivariate analysis confirmed the independent significant association between CD34 + MVD and survival (P = 0AE001).

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

“…8 The number of small vessels in a tumor, or MVD, is considered a surrogate indicator of angiogenesis. 4,22,24,33 The prognostic impact of MVD in hematological malignancies has been investigated by a number of groups, with conflicting results. 15,16,20,21,[23][24][25]30,31 In these studies, bone marrow microvessels are visualized by immunostaining of vascular endothelial cells; the stained microvessels are then counted and MVD determined.…”

“…Variations in immunostaining technique, such as the use of different primary antibodies among different laboratories, may be one factor. In contrast with Mesa et al, 8 who employed the clone HPCA-1 for CD34 immunostaining, we used the QBEND/10 clone, which has been extensively utilized by our group and other investigators to assess MVD 14,16,24,34 In addition, in our study, a different approach for MVD evaluation was used. Instead of numbering semiquantitatively vessels as done by Mesa et al, 8 we performed a complete count of all vessels in each section.…”

“…Instead of numbering semiquantitatively vessels as done by Mesa et al, 8 we performed a complete count of all vessels in each section. 24 This approach avoids the possible bias of selectively choosing areas with higher vascular density, and produces quantitative data without introducing predetermined arbitrary cutoffs or 'hot-spots'. It is noteworthy that the The differences observed in our study may be due to the different endothelial specificity of the two antibodies.…”

“…47 CD105 may represent a target for antiangiogenic therapy; 48 this belief is also supported by the concept that endothelial cells of tumor microvessels may be more susceptible to killing effects of anti-CD105 immunoconjugates than the vascular endothelium of normal tissues. 49 The prognostically significant increase of CD105-positive megakaryocytes in CIMF patients, in contrast to the absence in the marrows of lymphoproliferative disorders such as myeloma, 24 suggests a potential role for this MoAb as a target for abnormal cells of the megakaryocytic lineage. To confirm this hypothesis, CD105 expression needs to be studied in a wider range of myeloid disorders characterized by abnormal megakaryocytopoiesis, such as various leukemic conditions (eg acute megakaryoblastic leukemia) as well as in chronic myeloproliferative disorders and myelodysplastic syndromes.…”

Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

“…Increased angiogenesis was recently found to play a positive role in the growth of multiple types of hematological malignancies and is correlated with poor disease outcome [63]. Accumulating data show that angiogenesis occurs in the bone marrow of patients with MM [64] and that there is a direct correlation between increased angiogenesis and disease progression [65]. Pro-angiogenic factors include vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF).…”