Increased angiogenesis in chronic idiopathic myelofibrosis: vascular endothelial growth factor as a prominent...

Increased angiogenesis has been suggested to be implicated in the pathogenesis of chronic idiopathic myelofibrosis (CIMF). We hypothesized that vascular endothelial growth factor (VEGF) drives CIMF-associated angiogenesis, and thus, we aimed to determine its expression and biologic impact in newly diagnosed patients. All patients with CIMF diagnosed between 1990 and 2001, for whom adequate bone marrow specimens and clinical data were available, were deemed eligible. Each case was reclassified according to World Health Organization criteria. Microvessel density (MVD), as assessed by CD34 staining, and VEGF expression were examined by standard immunohistochemistry on paraffin-embedded trephine bone marrow biopsy specimens. The cytogenetic phenotype was determined by fluorescence in situ hybridization. Appropriate summary statistics were used for comparisons between groups; survival was calculated using Kaplan-Meier estimates. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. Fifty-five patients with CIMF were investigated. With a median of 43 vascular lumina per 0.747 mm(2), patients with CIMF displayed significantly greater MVD than did age-matched controls (n = 10; median MVD, 19; P < .001) with equal distribution between the various fibrosis stages. Moreover, VEGF expression was significantly increased in CIMF (median, 12 cells/0.747 mm(2) versus 1.4 cells/0.747 mm(2); P = .01) and correlated with MVD (P = .001). However, neither MVD nor VEGF expression correlated with cytogenetics or clinical outcome. We conclude that in CIMF, increased MVD is detectable even in early (pre-)fibrotic stages. Moreover, we found significantly elevated VEGF expression correlating with MVD, thus suggesting VEGF to play a prominent angiogenic role and representing a novel potential therapeutic target in CIMF.