Increased vascularization predicts favorable outcome in follicular lymphoma

Department of Hematology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Clinical Cancer Research (Impact Factor: 8.72). 02/2005; 11(1):154-61.
Source: PubMed


In malignant lymphoma, angiogenesis has been associated with adverse outcome or more aggressive clinical behavior. This correlation has been established in groups of patients with a large heterogeneity regarding lymphoma subtypes and treatment regimens. The aim of this study is to investigate the significance of vascularization in patients with follicular lymphoma receiving uniform first-line treatment.
We assessed microvessel density (MVD) in pretreatment lymph node biopsies of 46 previously untreated patients with follicular lymphoma using anti-CD34 immunohistochemical staining and interactive quantification. In a selection of cases, vascular endothelial growth factor (VEGF)-RNA in situ hybridization was done. Patients were treated with cyclophosphamide-vincristine-prednisone induction chemotherapy combined with IFN-alpha2b. Thirty-six patients responded and received IFN-alpha as maintenance therapy.
MVD ranged from 10 to 70 per measurement field of 0.19 mm2 (median, 38). Median progression-free survival was 47 months in patients with MVD in the highest tertile and only 13 months in patients with lower MVD. Overall survival in patients with low vessel density was 59 months. In patients with high vessel density, median overall survival was not reached. Multivariate analysis indicated that MVD was independently associated with overall survival. There was a lack of correlation between VEGF-RNA expression and vessel density.
This study shows that in follicular lymphoma increased vascularization is associated with improved clinical outcome. Furthermore, VEGF-A expression seems not to be involved in follicular lymphoma angiogenesis.

11 Reads
  • Source
    • "It affects several biological functions, including wide-ranging antiviral, antibacterial activities (Rönnblom et al., 1983), inhibition of tumour cell proliferation (Fidler et al., 1987) and improvement of immune functions. The remedial functions of IFNα2b have led to its approval as a potential agent for therapy of hairy cell leukaemia (Talpaz et al., 1986), chronic myelogenous leukaemia (Allan et al., 1995), gastrointestinal stromal tumours, chronic hepatitis B and C (Ariyasu et al., 2005), malignant melanoma, condylomata accuminata, follicular lymphoma (Koster et al., 2005) and AIDS-related Kaposi's sarcoma (Shepherd et al., 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human interferon alpha-2b (hIFNα2b) is the most important member of interferon family. Escherichia coli, yeast, mammalian cell cultures and baculovirus infected insect cells have been used for expressing recombinant human interferon. Recently Pichia pastoris based expression system has emerged as an attractive system for producing functional human recombinant IFNα2b. In this regard, gene dosage is considered, an important aspect to get the optimum expression of recombinant protein which may vary from one protein to another. In present study, we have shown the effect of IFNα2b gene dosage on extracellular expression of IFNα2b recombinant protein from P. pastoris. Constructs containing from one to five repeats of IFNα2b expressing cassettes were created via in vitro multimerization approach. P. pastoris host strain X-33 was transformed with these expression cassettes. Groups of P. pastoris clones transformed with different copies of IFNα2b expression cassette were screened for intrachromosomal integration. IFNα2b expression level of stable transformants was checked. Copy number of integrated IFNα2b was determined by performing qPCR of genomic DNA of recombinant P. patoris clones. It was observed that increase in copy number generally have positive effect on expression level of IFNα2b protein. Regarding the performance of multicopy strains, those obtained from transformation of multicopy vectors showed relatively high expression, compared to those generated using transformation vector having only one copy of IFNα2b. This was also observed that increase in drug resistance of a clone not guarantee its high expression, as integration of marker gene do not always correlate with integration of gene of interest. This article is protected by copyright. All rights reserved.
    Yeast 01/2014; 31(1). DOI:10.1002/yea.2990 · 1.63 Impact Factor
  • Source
    • "Other studies in NHL and in DLBCL found no correlation between MVD and VEGF expression [32] [33] [34]. On the contrary, an increased vascularity pretreatment predicted favorable outcome in terms of progression-free and overall survival in patients with FL who received chemotherapy in association with interferon-α2b [18], or in FL, a high MVD predicted progressive disease and overall survival and correlated with transformation to DLBCL [32] "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of angiogenesis in the growth of lymphomas and survival of patients with leukemias and other hematological malignancies has become evident since 1994. Angiogenic factors, such as vascular endothelial growth factor and its receptors together with other tumor microenvironment components, including myelo-monocytic cell, mast cells, endothelial progenitor cells, and circulating endothelial cells, have been shown to be important in the progression and maintenance of lymphoproliferative disorders. In this review article, we present an overview of the literature focusing on the relationship between angiogenesis and disease progression and the recent advantages in the antiangiogenic treatment in human non-Hodgkin lymphomas.
    Neoplasia (New York, N.Y.) 03/2013; 15(3):231-8. DOI:10.1593/neo.121962 · 4.25 Impact Factor
  • Source
    • "Survival of human patients suffering from lymphomas was not correlated with VEGFR-2 expression in some studies (Gratzinger et al., 2008; Tzankov et al., 2007), but VEGFR-2 expression was associated with a shorter survival time in a more recent study (Gratzinger et al., 2010). Survival of human patients mostly did not correlate with the MVD in lymphoma samples (Bairey et al., 2000; Gratzinger et al., 2010; Tzankov et al., 2007); however, in one study it was observed that increased vascularization was associated with improved clinical outcome in human follicular lymphoma (Koster et al., 2005). In another study, findings of remarkably high MVD in interfollicular areas of follicular lymphoma was linked to poorer overall survival (Jørgensen et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis, which is essential for malignancies to progress, depends on various signalling proteins including vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2). Microvessel density (MVD) is frequently used to evaluate angiogenesis. This study assessed the relationship between expression of VEGF, VEGFR-1 and VEGFR-2, MVD and the survival time in dogs with lymphoma. VEGF, VEGFR-1 and VEGFR-2 expression was evaluated immunohistochemically and microvessel profiles were counted in 34 lymphoma samples. Seventy-nine percent of the samples showed high VEGF expression and 62% were highly positive for VEGFR-1; VEGFR-2 immunoreactivity was mostly negative. Dogs treated with chemotherapy had a median survival time of 266days, but no significant relationships were found between overall survival time, MVD and expression of VEGF, VEGFR-1 or VEGFR-2. In this study, VEGF its receptors and the MVD were no prognostic factors in dogs with lymphoma.
    Research in Veterinary Science 05/2011; 92(3):444-50. DOI:10.1016/j.rvsc.2011.04.018 · 1.41 Impact Factor
Show more