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.
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).
Jørgensen
Judit M
JM
Department of Hematology, Aarhus University Hospital, Aarhus DK-8000, Denmark.
Sørensen
Flemming B
FB
Bendix
Knud
K
Nielsen
Johan L
JL
Funder
Anette
A
Karkkainen
Marika J
MJ
Tainola
Tapio
T
Sørensen
Annette B
AB
Pedersen
Finn S
FS
D'Amore
Francesco
F
D000368:Aged; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2