Phosphorylated VEGFR2/KDR receptors are widely expressed in B-cell non-Hodgkin's lymphomas and correlate with hypoxia inducible factor activation

✍ Scribed by Alexandra Giatromanolaki; Michael I. Koukourakis; Francesco Pezzella; Efthimios Sivridis; Helen Turley; Adrian L. Harris; Kevin C. Gatter

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 219 KB
• Volume: 26
• Category: Article
• ISSN: 0278-0232
• DOI: 10.1002/hon.861

✦ Synopsis

Abstract

The expression of hypoxia inducible factors (HIF) 1α and 2α, of vascular endothelial growth factor (VEGF) and of the phosphorylated form of its receptor VEGFR2 (pVEGFR2/KDR) were investigated immunohistochemically in a series of 146 B‐cell non‐Hodgkin's lymphomas and 48 normal lymph nodes. These proteins were significantly up‐regulated in neoplastic lymphocytes and a significantly higher expression of HIF1__α__ (p = 0.05), VEGF (p = 0.02) and pVEGFR2/KDR (p = 0.007) was recorded in diffuse large B‐cell lymphomas(DLBCL) compared to follicular lymphomas (FL). A strong statistical association of pVEGFR2/KDR expression with high HIF1__α__, HIF2__α__ and VEGF was noted in both DLBCL and FL. HIF1__α__ andHIF2__α__ were linked with VEGF expression but no association between HIF1__α__ and HIF2__α__ was noted. Vascular density was significantly higher in the lymphoma compared to normal tissue, but there was no association with any of the examined parameters. It is concluded that the VEGF/receptor pathway is active in more than half of NHLs and particularly in DLBCL. The intimate correlation of VEGF production with the presence of phosphorylated VEGF‐receptors strongly supports the concept of an autocrine pathway. The strong association of HIF__α__s with the expression of VEGF and pVEGFR2/KDR found in the study provide strong evidence on the role of HIF__α__s inthe activation of angiogenic and VEGF‐autocrine pathways that may be critical therapeutic targets for HIF‐inhibitors or other anti‐angiogenic agents. Copyright © 2008 John Wiley & Sons, Ltd.