Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade

Aims: Abnormalities involving proliferation, apoptosis, and angiogenesis are important in tumorigenesis. The purpose of this study was to examine these three biological processes, and their relation with the clinical stage and cytological grade in multiple myeloma (MM). Methods: Fifty four newly diagnosed patients with MM were studied by immunohistochemistry using bone marrow clot sections. Proliferation and apoptosis were evaluated for the proportion of MM cells (indicated by morphology and CD138 reactivity) positive for the Ki67 antigen and single stranded DNA (ssDNA), respectively, Angiogenesis was evaluated by measuring the intraturnoral microvessel density (IMVD) and by assessing the immunoreactivity of vascular endothelial growth factor (VEGF). Results: There were 30 men and 24 women (median age, 65 years; range, 37-84). At initial presentation, 15 (28%) were in Durie stage I, 15 (28%) in stage II, and 24 (44%) in stage III. Advanced clinical stage correlated with high cytological grade (p<0.03). The medians for Ki67, ssDNA, and IMVD were 4.4% (range, 0-15%), 0.2% (range, 0-2.8%), and 15.5 (range, 0-63), respectively. Among these three continuous parameters, the only significant correlation was that between Ki67 and IMVD (p<0.0001). Both Ki67 and IMVD also correlated with the clinical stage, cytological grade, and VEGF positivity (p<0.05). No correlation was found between ssDNA and all of the other parameters. Conclusions: These data suggest that proliferation is associated with angiogenesis in MM. Furthermore, proliferation and angiogenesis, but not apoptosis, may be important in disease progression. Lastly, increased production of VEGF may be one of the contributing factors to the increase in intraturnoral vascularity seen in advanced MM.