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

• Published in: Laboratory investigation Vol. 88; no. 1; pp. 38 - 47
• Main Authors: 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 S, Natkunam, Yasodha
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.01.2008; Nature Publishing Group US; Nature Publishing; Nature Publishing Group
• Subjects: angiogenesis; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols; Biological and medical sciences; Biotechnology; Blood Vessels - pathology; Cohort Studies; diffuse large B-cell lymphoma; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Laboratory Medicine; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Medical sciences; Medicine; Medicine & Public Health; Pathology; Prognosis; Receptors, Vascular Endothelial Growth Factor - metabolism; research-article; Signal Transduction; Tissue Array Analysis; Vascular Endothelial Growth Factor A - metabolism; VEGF; VEGF receptor 1; VEGF receptor 2; VEGF receptor 2; diffuse large B-cell lymphoma; angiogenesis; VEGF; VEGF receptor 1; Biotechnology; Prognosis; B cell neoplasm; Malignant hemopathy; Density; Angiogenesis; Microcirculation; Chemotherapy; Vascular endothelium growth factor; Treatment; Lymphoproliferative syndrome; Clinical biology; Diffuse large B cell lymphoma; Anthracyclins; Neovascularization; Cancer; Biological receptor
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700697

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.