Evaluation of Angiogenesis in Multiple Myeloma by VEGF Immunoexpression and Microvessel Density

Abstract

Background Multiple myeloma (MM) is a plasma cell disorder characterized by monoclonal proliferation of plasma cells in bone marrow. Plasmablastic MM is a morphologic subset of MM, containing ≥2% plasmablasts of all plasma cells. Methods The study included 30 consecutively diagnosed patients of MM (6 plasmablastic, 24 nonplasmablastic) over a span of 2 years. Angiogenesis in MM was assessed by analysis of vascular endothelial growth factor (VEGF) immunoexpression by plasma cells and microvessel density (MVD) using anti-CD34 antibody. CD34 and VEGF immunohistochemical staining was performed in all the 30 cases. Angiogenesis was studied in relation to plasmablastic morphology and clinical profile to determine if any correlation exists between these. Results The mean VEGF expression of 80.83 ± 7.36 in plasmablastic myeloma cases was significantly higher compared with a mean VEGF of 53.54 ±17.09 in nonplasmablastic cases. Most of the cases (66.6%) of plasmablastic myeloma exhibited strong (3+) VEGF expression. The difference in mean VEGF expression between plasmablastic and nonplasmablastic cases was found to be statistically significant (p = 0.001). The mean MVD in plasmablastic cases was 44.8 ± 3.69, while in the nonplasmablastic category, the mean MVD was 23.7 ± 5.14, difference being statistically significant (p < 0.05). Also, a positive correlation was found between VEGF expression and MVD. Conclusion A moderate/strong VEGF intensity and higher MVD were found in cases of plasmablastic MM, suggesting that a more aggressive histological disease may be associated with increased production of VEGF. This finding might be helpful to identify a subset of patients with adverse prognosis and to provide antiangiogenic therapy to improve their survival. However, studies comprising larger number of patients are required to bring out a statistical significance to further substantiate these findings.

Immunohistochemical Study of Tumor Associated-Macrophages and Microvessel Density in Multiple Myeloma

“…This was consistent with Rana et al In the present study, it was revealed that MVD increased with immaturity of plasma cells. It was supported by Palta et al [8].…”

“…Additional evidence indicates that angiogenesis in bone marrow corresponds with the production of neoplastic plasma cells and has a critical role in the course of disease [8].…”

“…The median extent of infiltration (40/HPF field) in each histologic site was utilized to differentiate between individuals with low and high TAM density [7]. And according to MVD, MVD less than 20 /HPF was designated as low grade and equal or greater than 20 /HPF as high grade [8].…”

Mechanism of Targeting the Hedgehog Signaling Pathway against Chemotherapeutic Resistance in Multiple Myeloma

“…Multiple myeloma cells can bind to cellulose in the microenvironment and generate cell adhesion-mediated chemotherapeutic drug resistance. However, cytokines such as IL-6 and VEGF can induce the activation of a variety of signaling pathways and promote cell adhesion-mediated drug resistance, thus promoting the proliferation of multiple myeloma cells and inhibiting cell apoptosis [ 24 , 25 ].…”

The yin–yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma

“…Another research found that most of the MM cases exhibited strong VEGF expression. Also, VEGF expression is positively correlated to MVD ( 138 ). VEGF and its type 2 receptor (VEGFR2) polymorphisms are related to the increased risk and aggressiveness in MM ( 139 ).…”