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Angiogenesis in nodal B cell lymphomas: a high throughput study
  1. Alexandar Tzankov1,
  2. Simone Heiss1,
  3. Stephanie Ebner1,
  4. William Sterlacci1,
  5. Georg Schaefer1,
  6. Florian Augustin2,
  7. Michael Fiegl2,
  8. Stephan Dirnhofer3
  1. 1Institute of Pathology, Medical University of Innsbruck, Innsbruck, Austria
  2. 2Department of Hematology, Medical University of Innsbruck, Innsbruck, Austria
  3. 3Institute of Pathology, University Hospital Basel, Basel, Switzerland
  1. Correspondence to:
 Dr A Tzankov
 Institute of Pathology, Medical University of Innsbruck, Müllerstr 44, A-6020 Innsbruck, Austria; atzankov{at}


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.