Expression level, tissue distribution pattern, and prognostic impact of vascular endothelial growth factors VEGF and VEGF-C and their receptors Flt-1, KDR, and Flt-4 in different subtypes of non-Hodgkin lymphomas

Judit M Jørgensen; Flemming B Sørensen; Knud Bendix; Johan L Nielsen; Anette Funder; Marika J Karkkainen; Tapio Tainola; Annette B Sørensen; Finn S Pedersen; Francesco D'Amore

doi:10.1080/10428190903156729

Expression level, tissue distribution pattern, and prognostic impact of vascular endothelial growth factors VEGF and VEGF-C and their receptors Flt-1, KDR, and Flt-4 in different subtypes of non-Hodgkin lymphomas

Leuk Lymphoma. 2009 Oct;50(10):1647-60. doi: 10.1080/10428190903156729.

Authors

Judit M Jørgensen¹, Flemming B Sørensen, Knud Bendix, Johan L Nielsen, Anette Funder, Marika J Karkkainen, Tapio Tainola, Annette B Sørensen, Finn S Pedersen, Francesco D'Amore

Affiliation

¹ Department of Hematology, Aarhus University Hospital, Aarhus DK-8000, Denmark.

PMID: 19701853
DOI: 10.1080/10428190903156729

Abstract

The aim of the study was to investigate the expression of angio- and lymphangiogenic molecules (vascular endothelial growth factors VEGF and VEGF-C and their receptors Flt-1, KDR, and Flt-4) in non-Hodgkin lymphomas (NHL) treated in the pre-rituximab era. Pre-therapeutic lymph-node biopsies from 155 patients with NHL (64 follicular lymphomas (FLs), 47 de novo diffuse large B-cell lymphomas (DLBCL) and 44 peripheral T-cell lymphomas (PTCL)) were stained by in situ hybridization and immunohistochemistry. Tumor cell expression of VEGF, VEGF-C and their receptors was detected in most of the analyzed biopsies. In FL, diffuse intratumoral VEGF staining correlated with shorter overall survival (OS) (p = 0.008) and diffuse KDR staining was associated with a higher risk of histologic transformation (p = 0.05). In DLBCL, high KDR expression predicted poor treatment response (p = 0.03) and had a significant adverse impact on OS (p < 0.001). In PTCL, diffuse tissue distribution of VEGF mRNA correlated with an unfavorable 5-year OS (p = 0.004).

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cell Nucleus / chemistry
Cytoplasm / chemistry
Female
Gene Expression Profiling
Humans
Lymph Nodes / chemistry
Lymph Nodes / pathology
Lymphoma, Follicular / genetics*
Lymphoma, Follicular / mortality
Lymphoma, Follicular / pathology
Lymphoma, Large B-Cell, Diffuse / genetics*
Lymphoma, Large B-Cell, Diffuse / mortality
Lymphoma, Large B-Cell, Diffuse / pathology
Lymphoma, T-Cell, Peripheral / genetics*
Lymphoma, T-Cell, Peripheral / mortality
Lymphoma, T-Cell, Peripheral / pathology
Male
Middle Aged
Neoplasm Proteins / analysis*
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neovascularization, Pathologic / etiology
Neovascularization, Pathologic / genetics
Prognosis
RNA, Messenger / analysis
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
RNA, Neoplasm / analysis
RNA, Neoplasm / biosynthesis
RNA, Neoplasm / genetics
Retrospective Studies
Vascular Endothelial Growth Factor A / analysis*
Vascular Endothelial Growth Factor A / biosynthesis
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor C / analysis*
Vascular Endothelial Growth Factor C / biosynthesis
Vascular Endothelial Growth Factor C / genetics
Vascular Endothelial Growth Factor Receptor-1 / analysis*
Vascular Endothelial Growth Factor Receptor-1 / biosynthesis
Vascular Endothelial Growth Factor Receptor-1 / genetics
Vascular Endothelial Growth Factor Receptor-2 / analysis*
Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
Vascular Endothelial Growth Factor Receptor-2 / genetics

Substances

Neoplasm Proteins
RNA, Messenger
RNA, Neoplasm
VEGFA protein, human
VEGFC protein, human
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2