Expression of VEGF and microvessel density in patients with multiple myeloma: clinical and prognostic significance

Abstract

The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was estimated by counting the number of microvessels in three "hot spots" at 400x magnification. VEGF immunoreactivity was estimated on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity). No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29 vs. 34 months, P = 0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three "hot spots". There was significant correlation between MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (> or = 15) (46 vs. 22 months, P = 0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone and a predictor of poor survival in newly diagnosed myeloma.

Notch1 overexpression promotes cell growth and tumor angiogenesis in myeloma

“…It was reported VEGF was responsible for the development, maintenance, and progression of MM by promoting bone marrow angiogenesis [29]. More recently, it was shown that MVD was a poor prognostic factor in multiple myeloma [30]. Our results showed that Notch1 overexpression was associated with increased VEGF expression and MVD.…”

Bisphosphonates Induce Apoptosis of Circulating Endothelial Cells in Multiple Myeloma Patients and in Subjects with Bisphosphonate-Induced Osteonecrosis of the Jaws

“…In the previous paper, the population examined was in fact heterogeneous and included MM subjects and patients with breast cancer who were treated with exemestane, capecitabine or radiotherapy. Moreover, it is well known that in MM patients, there is a significant correlation between angiogenesis and the extent of bone marrow infiltration or proliferative activity, and the different amounts of CECs could reflect a different biological potency of a malignant clone [22,23]. Ria et al [24 ]pointed out that microenvironmental factors (such as hypoxia, inflammation, expression of multiple cytokines and growth factors) regulating tumor-associated blood vessels may induce changes in the proliferation and apoptotic potential even in the same patient.…”

EVALUATION OF p300 AND VEGF EXPRESSION AND MICROVESSEL DENSITY IN PLASMA CELL MYELOMA

“…owever, despite a statistically significant relationship between EGF expression and the S, expression of EGF was not considered to be an independent prognostic factor in a past study among PCM patients 8 . Also no significant di erence was reported between EGF-positive and EGF-negative patients with PCM in terms of overall survival in another study 24 . Bone marrow M D was not found to be significantly correlated with S both at diagnosis and prior to transplant 3 and no correlation was noted between baseline bone marrow M D and PFS and S in PCM patients 25 .…”