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 S. Lossos, Yasodha Natkunam

Research output: Contribution to journalArticle

78 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Gratzinger, D., Zhao, S., Tibshirani, R. J., Hsi, E. D., Hans, C. P., Pohlman, B., Bast, M., Avigdor, A., Schiby, G., Nagler, A., Byrne, G. E., Lossos, I. S., & 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, 88(1), 38-47. https://doi.org/10.1038/labinvest.3700697