Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy

Dita Gratzinger, Shuchun Zhao, Robert J. Tibshirani, Eric D. Hsi, Christine P. Hans, Brad Pohlman, Martin Bast, Abraham Avigdor, Ginette Schiby, Arnon Nagler, Gerald E. Byrne, Izidore Lossos, Yasodha Natkunam

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Vascular endothelial growth factor-mediated signaling has at least two potential roles in diffuse large B cell lymphoma: potentiation of angiogenesis, and potentiation of lymphoma cell proliferation and/or survival induced by autocrine vascular endothelial growth factor receptor-mediated signaling. We have recently shown that diffuse large B cell lymphomas expressing high levels of vascular endothelial growth factor protein also express high levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2. We have now assessed a larger multi-institutional cohort of patients with de novo diffuse large B cell lymphoma treated with anthracycline-based therapy to address whether tumor vascularity, or expression of vascular endothelial growth factor protein and its receptors, contribute to patient outcomes. Our results show that increased tumor vascularity is associated with poor overall survival (P=0.047), and is independent of the international prognostic index. High expression of vascular endothelial growth factor receptor-1 by lymphoma cells by contrast is associated with improved overall survival (P=0.044). The combination of high vascular endothelial growth factor and vascular endothelial growth factor receptor-1 protein expression by lymphoma cells identifies a subgroup of patients with improved overall (P=0.003) and progression-free (P=0.026) survival; these findings are also independent of the international prognostic index. The prognostic significance of overexpression of this ligand-receptor pair suggests that autocrine signaling via vascular endothelial growth factor receptor-1 may represent a survival or proliferation pathway in diffuse large B cell lymphoma. Dependence on autocrine vascular endothelial growth factor receptor-1-mediated signaling may render a subset of diffuse large B-cell lymphomas susceptible to anthracycline-based therapy.

Original languageEnglish
Pages (from-to)38-47
Number of pages10
JournalLaboratory Investigation
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2008

Fingerprint

Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor
Lymphoma, Large B-Cell, Diffuse
Anthracyclines
Microvessels
Vascular Endothelial Growth Factor A
Drug Therapy
Lymphoma
Survival
Autocrine Communication
Vascular Endothelial Growth Factor Receptor-2
Proteins
Neoplasms
Cell Survival
Cell Proliferation
Ligands
Therapeutics

Keywords

  • Angiogenesis
  • Diffuse large B-cell lymphoma
  • VEGF
  • VEGF receptor 1
  • VEGF receptor 2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy. / Gratzinger, Dita; Zhao, Shuchun; Tibshirani, Robert J.; Hsi, Eric D.; Hans, Christine P.; Pohlman, Brad; Bast, Martin; Avigdor, Abraham; Schiby, Ginette; Nagler, Arnon; Byrne, Gerald E.; Lossos, Izidore; Natkunam, Yasodha.

In: Laboratory Investigation, Vol. 88, No. 1, 01.01.2008, p. 38-47.

Research output: Contribution to journalArticle

Gratzinger, D, Zhao, S, Tibshirani, RJ, Hsi, ED, Hans, CP, Pohlman, B, Bast, M, Avigdor, A, Schiby, G, Nagler, A, Byrne, GE, Lossos, I & Natkunam, Y 2008, 'Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy', Laboratory Investigation, vol. 88, no. 1, pp. 38-47. https://doi.org/10.1038/labinvest.3700697
Gratzinger, Dita ; Zhao, Shuchun ; Tibshirani, Robert J. ; Hsi, Eric D. ; Hans, Christine P. ; Pohlman, Brad ; Bast, Martin ; Avigdor, Abraham ; Schiby, Ginette ; Nagler, Arnon ; Byrne, Gerald E. ; Lossos, Izidore ; Natkunam, Yasodha. / Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy. In: Laboratory Investigation. 2008 ; Vol. 88, No. 1. pp. 38-47.
@article{de4066fd8e474bc589034d2c8146bb1c,
title = "Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy",
abstract = "Vascular endothelial growth factor-mediated signaling has at least two potential roles in diffuse large B cell lymphoma: potentiation of angiogenesis, and potentiation of lymphoma cell proliferation and/or survival induced by autocrine vascular endothelial growth factor receptor-mediated signaling. We have recently shown that diffuse large B cell lymphomas expressing high levels of vascular endothelial growth factor protein also express high levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2. We have now assessed a larger multi-institutional cohort of patients with de novo diffuse large B cell lymphoma treated with anthracycline-based therapy to address whether tumor vascularity, or expression of vascular endothelial growth factor protein and its receptors, contribute to patient outcomes. Our results show that increased tumor vascularity is associated with poor overall survival (P=0.047), and is independent of the international prognostic index. High expression of vascular endothelial growth factor receptor-1 by lymphoma cells by contrast is associated with improved overall survival (P=0.044). The combination of high vascular endothelial growth factor and vascular endothelial growth factor receptor-1 protein expression by lymphoma cells identifies a subgroup of patients with improved overall (P=0.003) and progression-free (P=0.026) survival; these findings are also independent of the international prognostic index. The prognostic significance of overexpression of this ligand-receptor pair suggests that autocrine signaling via vascular endothelial growth factor receptor-1 may represent a survival or proliferation pathway in diffuse large B cell lymphoma. Dependence on autocrine vascular endothelial growth factor receptor-1-mediated signaling may render a subset of diffuse large B-cell lymphomas susceptible to anthracycline-based therapy.",
keywords = "Angiogenesis, Diffuse large B-cell lymphoma, VEGF, VEGF receptor 1, VEGF receptor 2",
author = "Dita Gratzinger and Shuchun Zhao and Tibshirani, {Robert J.} and Hsi, {Eric D.} and Hans, {Christine P.} and Brad Pohlman and Martin Bast and Abraham Avigdor and Ginette Schiby and Arnon Nagler and Byrne, {Gerald E.} and Izidore Lossos and Yasodha Natkunam",
year = "2008",
month = "1",
day = "1",
doi = "10.1038/labinvest.3700697",
language = "English",
volume = "88",
pages = "38--47",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy

AU - Gratzinger, Dita

AU - Zhao, Shuchun

AU - Tibshirani, Robert J.

AU - Hsi, Eric D.

AU - Hans, Christine P.

AU - Pohlman, Brad

AU - Bast, Martin

AU - Avigdor, Abraham

AU - Schiby, Ginette

AU - Nagler, Arnon

AU - Byrne, Gerald E.

AU - Lossos, Izidore

AU - Natkunam, Yasodha

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Vascular endothelial growth factor-mediated signaling has at least two potential roles in diffuse large B cell lymphoma: potentiation of angiogenesis, and potentiation of lymphoma cell proliferation and/or survival induced by autocrine vascular endothelial growth factor receptor-mediated signaling. We have recently shown that diffuse large B cell lymphomas expressing high levels of vascular endothelial growth factor protein also express high levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2. We have now assessed a larger multi-institutional cohort of patients with de novo diffuse large B cell lymphoma treated with anthracycline-based therapy to address whether tumor vascularity, or expression of vascular endothelial growth factor protein and its receptors, contribute to patient outcomes. Our results show that increased tumor vascularity is associated with poor overall survival (P=0.047), and is independent of the international prognostic index. High expression of vascular endothelial growth factor receptor-1 by lymphoma cells by contrast is associated with improved overall survival (P=0.044). The combination of high vascular endothelial growth factor and vascular endothelial growth factor receptor-1 protein expression by lymphoma cells identifies a subgroup of patients with improved overall (P=0.003) and progression-free (P=0.026) survival; these findings are also independent of the international prognostic index. The prognostic significance of overexpression of this ligand-receptor pair suggests that autocrine signaling via vascular endothelial growth factor receptor-1 may represent a survival or proliferation pathway in diffuse large B cell lymphoma. Dependence on autocrine vascular endothelial growth factor receptor-1-mediated signaling may render a subset of diffuse large B-cell lymphomas susceptible to anthracycline-based therapy.

AB - Vascular endothelial growth factor-mediated signaling has at least two potential roles in diffuse large B cell lymphoma: potentiation of angiogenesis, and potentiation of lymphoma cell proliferation and/or survival induced by autocrine vascular endothelial growth factor receptor-mediated signaling. We have recently shown that diffuse large B cell lymphomas expressing high levels of vascular endothelial growth factor protein also express high levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2. We have now assessed a larger multi-institutional cohort of patients with de novo diffuse large B cell lymphoma treated with anthracycline-based therapy to address whether tumor vascularity, or expression of vascular endothelial growth factor protein and its receptors, contribute to patient outcomes. Our results show that increased tumor vascularity is associated with poor overall survival (P=0.047), and is independent of the international prognostic index. High expression of vascular endothelial growth factor receptor-1 by lymphoma cells by contrast is associated with improved overall survival (P=0.044). The combination of high vascular endothelial growth factor and vascular endothelial growth factor receptor-1 protein expression by lymphoma cells identifies a subgroup of patients with improved overall (P=0.003) and progression-free (P=0.026) survival; these findings are also independent of the international prognostic index. The prognostic significance of overexpression of this ligand-receptor pair suggests that autocrine signaling via vascular endothelial growth factor receptor-1 may represent a survival or proliferation pathway in diffuse large B cell lymphoma. Dependence on autocrine vascular endothelial growth factor receptor-1-mediated signaling may render a subset of diffuse large B-cell lymphomas susceptible to anthracycline-based therapy.

KW - Angiogenesis

KW - Diffuse large B-cell lymphoma

KW - VEGF

KW - VEGF receptor 1

KW - VEGF receptor 2

UR - http://www.scopus.com/inward/record.url?scp=37549055122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37549055122&partnerID=8YFLogxK

U2 - 10.1038/labinvest.3700697

DO - 10.1038/labinvest.3700697

M3 - Article

C2 - 17998899

AN - SCOPUS:37549055122

VL - 88

SP - 38

EP - 47

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 1

ER -