Increased vascularization predicts favorable outcome in follicular lymphoma.
ABSTRACT 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.
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ABSTRACT: The clinical course and therapy of mantle cell lymphoma (MCL) are heterogeneous and often unsatisfactory. Prognostic factors are needed to stratify the patients. Microvessel density (MVD) has prognostic significance in some malignancies. There is little information about the vasculature of MCL, although some antiangiogenic drugs are in use. We studied MVD using systematic uniform random sampling and unbiased counting frames in immunohistochemical reactions with anti-CD34 antibody in pre-therapeutic extramedullary MCL samples of 177 patients. We analyzed the relationship of MVD to overall survival (OS) and progression-free survival (PFS), as well as to proliferative activity (Ki-67), mantle cell lymphoma prognostic index (MIPI), morphological variant, pattern of growth, and localization. MVD varied widely: range 54.6-503.6 vessels/mm(2), median 158.2 vessels/mm(2). Higher MVD was associated with bone marrow infiltration at the time of diagnosis (P = 0.001). High MVD was associated with significantly worse OS (P = 0.04) only in patients treated with non-intensive (conventional) therapy. MVD correlated positively with MIPI scores but not with the proliferation, morphological variant, growth pattern, or localization. Univariate analysis identified a prognostic influence of morphological variant, MIPI, and proliferative activity on OS and PFS and a prognostic influence of bone marrow infiltration at the time of diagnosis on PFS. Multivariate analysis showed prognostic influence of MIPI and proliferative activity on OS and PFS only. In conclusion, this is the first clinicopathological study of MVD of MCL with long-term follow-up showing negative prognostic trends of high MVD in MCL and positive correlation of MVD and MIPI.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2014; · 2.56 Impact Factor
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ABSTRACT: Observation until the development of symptoms, or ‘watch and wait’, has long been a proposed management technique for patients with indolent lymphomas. However, investigators have found that there may be differences in outcomes for various patient groups according to histopathology, clinical features of the disease, biologic factors as yet to be fully recognized, and type of initial therapy offered. Recently, investigators from the UK National Cancer Research Institute reported that progression-free results were significantly improved when asymptomatic patients with indolent follicular lymphomas received initial therapy with single-agent rituximab rather than when they underwent observation alone. These results were further improved when they received maintenance rituximab. Time to chemotherapy was also longer when these patients received initial therapy with rituximab, thereby delaying the need for such treatment. However, overall survival rates for patients who received rituximab as initial therapy were similar to those for patients who underwent initial ‘watch and wait’. Future studies should concentrate on risks of such management, including cost effectiveness of such treatments and development of resistance to subsequent therapies.BioDrugs 12/2012; 26(6). · 2.12 Impact Factor
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ABSTRACT: Human lymphomas usually develop in specialized tissue microenvironments characterized by different populations of accessory stromal and lymphoid cells that interact with malignant cells. A clinical role of the tumor microenvironment has recently emerged, bringing new knowledge and suggesting new ideas and targets for treatment. This chapter analyzes the microenvironment in human lymphomas highlighting the role of inflammation in their pathogenesis. Microenvironmental specificity is detailed according to different models including classic Hodgkin lymphoma (HL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma, unspecified and angioimmunoblastic T-cell lymphoma (AITL).Advances in Experimental Medicine and Biology 01/2014; 816:315-33. · 2.01 Impact Factor