Aim: To assess the biological significance of vascular endothelial growth factor (VEGF) A, VEGF receptor (Flk-1) and cyclooxygenase 2 (COX2) expression with respect to microvessel density (MVD), proliferative activity (Ki-67), expression of p53 and clinical presentation in a large cohort of nodal B cell lymphomas.
Methods: An immunohistochemical and morphometric study was performed on a validated tissue microarray containing 271 B cell lymphoma specimens, 197 of which included follow-up data. Statistical assessment was done by Pearson’s χ2 test, Spearman’s rank correlation coefficient, analysis of variance and survival analysis.
Results: 266 (98%) cases were evaluable. Strong VEGF expression was observed in only 20 diffuse large B cell lymphomas (DLBCLs). Flk-1 and COX2 were expressed in 53 and 21 cases, respectively, mainly in DLBCLs, follicular lymphoma (FL) grade 3 and mantle cell lymphomas (MCLs), in a low proportion of cells. MVD decreased in the following order: DLBCLs, FLs, MCLs and small lymphocytic lymphomas/chronic lymphocytic leukaemia (SLL/CLLs). VEGF expression correlated with Ki-67, p53 and COX2 expression in the whole cohort and in DLBCLs. Flk-1 expression correlated with Ki-67 in the cohort and in SLL/CLL and FL grade 1 and 2. COX2 expression correlated with Ki-67 and p53. The analysed angiogenesis parameters did not correlate with clinical parameters or survival.
Conclusions: Angiogenesis plays a differential role in various B cell lymphomas. Aggressive lymphomas express the potential molecular therapeutic targets VEGF and COX2, and have higher MVD. In a few low proliferation-fraction lymphomas, Flk-1 might have a role in proliferative advantage. Therapeutic strategies aimed at angiogenesis should take into account lymphoma heterogeneity.
- COX2, cyclooxygenase 2
- DLBCL, diffuse large B cell lymphoma
- FL, follicular lymphoma
- FL G1&2, FL grade 1 and 2
- MCL, mantle cell lymphoma
- MVD, microvessel density
- SLL/CLL, small lymphocytic lymphoma/chronic lymphocytic leukaemia
- TMA, tissue microarray
- VEGF, vascular endothelial growth factor
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Published Online First 21 June 2006
Competing interests: None declared.