Clinical and histopathological study of angiogenesis in multiple myeloma

Abstract

Purpose: Angiogenesis is an essential component in the growth and progression of multiple myeloma (MM). We studied the clinical significance of angiogenesis in patients with MM estimated by precise counting of the number of vessels (i.e. microvessel density, MVD) and compared these results with the results obtained using semi-quantitative grading of angiogenesis. Methods: Fifty-nine newly diagnosed cases of MM were analyzed with respect to clinical features, laboratory findings, histological features, angiogenesis parameters, and response to treatment. Bone marrow microvessels were examined using immunohistochemical staining for CD34. Bone marrow angiogenesis was estimated by two different methods. The mean number of vessels per area in each sample was characterized as the MVD. Microvessels were counted manually on light microscopy in 3 hot spots at x400 magnification. Semi-quantitative estimation of angiogenesis was based on visual assessment of slides at x100 magnification. Each slide was assigned as low, intermediate or high intensity of angiogenesis. Results: The median MVD was 15 vessels per 3 hot spots (range 1-89). Intensity of angiogenesis was assigned as low in 24 (40.7%) patients, intermediate in 17 (28.8%) and high in 18 (30.5%). Significant correlation between intensity of angiogenesis (estimated using both methods) and histological grade, extent of bone marrow infiltration, proliferative activity of myeloma cells and poor survival was found. Semi-quantitatively assessed intensity of angiogenesis additionally correlated with clinical stage. There was a statistically highly significant correlation between MVD and semi-quantitatively estimated intensity of angiogenesis (p <0.001). Conclusion: Tumor-associated angiogenesis is an important prognostic feature in MM and should be routinely done on bone marrow biopsies of these patients. Simple semi-quantitative grading of angiogenesis can be recommended for daily practice, as an alternative method for complicated and time-consuming estimation of MVD. © 2011 Zerbinis Medical Publications.