Prognostic significance of vascular endothelial growth factor immunoexpression in the context of adverse standard prognostic factors in multiple myeloma.

Abstract

Vascular endothelial growth factor (VEGF) acts in several steps of multiple myeloma (MM) pathogenesis and it is an important mediator of tumor angiogenesis. The aim of this study was to examine the prognostic significance of VEGF immunoexpression in the context of standard prognostic factors present in a cohort of advanced MM patients. Fifty untreated MM patients were enrolled from May 2000 to December 2002. Bone marrow sections were subjected to morphologic assessment and immunohistochemical studies with antibodies against CD34 and VEGF. Angiogenesis was measured by microvessel density (MVD) and stratified into high (MVD > or = 20) and low angiogenesis status (MVD < 20). VEGF immunoreactivity was examined on the basis of intensity and percentage of positive plasma cells (PC). Ninety-four percent of patients presented advanced disease at diagnosis. Median PC marrow infiltration was 80%. Twelve percent of patients presented plasmablastic morphology. Low angiogenesis was present in 27% of patients, while high angiogenesis was present in 73%. Twenty-nine percent of patients had VEGF < 10% and 71% had VEGF > or = 10%. Weak-intensity VEGF was observed in 34% of cases, while 37% had moderate/strong VEGF intensity. Although VEGF had prognostic impact on overall survival (OS) and event-free survival (EFS) in univariate analysis, multivariate analysis identified only plasmablastic morphology and elevated serum lactate dehydrogenase (LDH) level as independent prognostic factors to predict OS (P = 0.04 and P = 0.02, respectively). With regard to EFS, although VEGF showed statistical trend to influence survival (P = 0.08), the parameters of independent prognostic value were also plasmablastic morphology (P = 0.01) and elevated LDH level (P = 0.01). Our findings underline the frequent expression of VEGF in advanced-stage MM and the greater prognostic information of simple and readily available factors, namely plasmablastic morphology and elevated LDH. Moreover, despite the absence of prognostic importance in multivariate analysis, VEGF and its receptors remain promising therapeutic targets in MM.