Vascularization predicts overall survival and risk of transformation in follicular lymphoma

Follicular lymphoma patients display heterogeneous overall survival and variable risk of transformation. Recent studies have highlighted the role of the microenvironment. The contribution of microvessel density to follicular lymphoma survival remains controversial. We used a quantitative tumor mapping approach to determine whether the degree of vascularization correlated with outcome in a uniformly treated cohort. Whole-tissue sections of diagnostic biopsies from 84 cases were stained for CD34 and tumor-to-vessel-distance that encompassed 90% of the tumor (TVD(90)) was determined using image analysis. Twenty-one cases with lower TVD(90) showed inferior overall survival (P=0.0001) and high risk of transformation (P=0.01). These cases significantly correlated with increased Lymphoma-Associated Macrophages (χ(2)=0.025). In multivariate analysis macrophages content, IPI and TVD(90) were independent predictors of overall survival (P=0.05, P=0.001 and P=0.01, respectively) and IPI and TVD(90) predicted risk of transformation (P=0.008 and P=0.08, respectively). Increased angiogenesis is an independent marker of inferior survival and may promote transformation.