Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients

Abstract

High serum concentrations of vascular endothelial growth factor (S-VEGF) and basic fibroblast growth factor (S-bFGF) are associated with unfavorable clinical characteristics in cancer. The combined effect of S-VEGF and S-bFGF on the survival of 200 patients with non-Hodgkin lymphoma (NHL) was studied. High S-VEGF and S-bFGF at diagnosis were associated with poor survival with the medians, the highest tertiles, or the highest quartiles as the cutoff values. The highest prognostic power was obtained when S-VEGF and S-bFGF were examined as a combination. Patients who had both S-VEGF and S-bFGF within the highest quartiles had only a 21% 5-year survival rate in contrast to a 64% 5-year survival rate among patients with both factors within the 3 lowest quartiles (P < .0001). Simultaneous elevation of S-VEGF and S-bFGF was associated with poor survival in different grades of lymphomas and in the largest histologic subgroup, the large-cell diffuse and immunoblastic lymphomas. S-VEGF (relative risk [RR], 1.83; P = .019) and S-bFGF (RR, 2.02; P = .0049) had independent influences on survival in multivariate models when tested together with the components of the International Prognostic Index (IPI). Patients with both S-VEGF and S-bFGF within the highest quartiles had nearly 3 times higher risk for death (RR, 2.90; 95% confidence interval [CI], 1.56-5.40;P = .0008) than the rest of the patients. This RR was higher than the relative risks associated with any of the components of the IPI in the same model. The authors conclude that the combination of S-VEGF and S-bFGF is a powerful prognostic variable in NHL.

VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma

“…(12,13) Moreover, angiogenesis has been associated with adverse outcomes and more aggressive behavior of malignant lymphomas. (14,15) There is substantial inherited genetic variability within VEGF and one of its receptors, VEGF receptor 2 (VEGFR2), including multiple single nucleotide polymorphisms (SNP). The level of VEGF expression varies depending on the presence of a genetic polymorphism.…”

Endotoxins induce and interferon‐α suppresses vascular endothelial growth factor (VEGF) production in human peripheral blood mononuclear cells

“…In a nude mouse model, VEGF increases angiogenesis (4-6), a prerequisite for solid tumor growth beyond a few cubic millimeters in volume (7), and VEGF antibodies inhibit the growth of tumor cell lines in vivo (8)(9)(10). In patients with cancer, high serum VEGF levels serve as markers of progressive or extensive disease (11)(12)(13)(14)(15) and poor prognosis (16)(17)(18). Elevated serum levels of VEGF have also been associated with disease activity in rheumatoid arthritis (19,20), Crohn's disease (21), and ulcerative colitis (21), as well as in angiogenic conditions such as pregnancy (22) and pre-eclampsia (23).…”

The Vascular Endothelial Growth Factor (VEGF) Signaling Pathway: A Therapeutic Target in Patients with Hematologic Malignancies

“…Elevated levels of angiogenic growth factors are also associated with an adverse prognosis in patients with non-Hodgkin's lymphoma (NHL). In a single-institution study of 200 patients, levels of serum VEGF were negatively correlated with prognosis [34]. However, the highest prognostic power was observed when VEGF and serum bFGF levels were examined in combination.…”

“…Significantly elevated levels of VEGF are observed in a variety of hematologic malignancies [7,10,34]. A study of 417 patients showed similarly elevated levels of VEGF in patients with AML (n = 115) and advanced MDS (n = 40) compared with controls [7].…”

“…Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies. The Oncologist 2001;6(suppl 5): [32][33][34][35][36][37][38][39]…”