Expression of vascular endothelial growth factor in lymphomas and castleman's disease

Abstract

Vascular endothelial growth factor (VEGF) is one of the main angiogenic cytokines in human solid tumours and inhibition of VEGF‐induced angiogenesis suppresses tumour growth. Some groups of malignant lymphoma, including peripheral T‐cell lymphomas and Hodgkin's disease, are characterized by a conspicuous proliferation of small vessels. To test the hypothesis that VEGF may also be involved in the angiogenesis in lymphomas and other lesions of the lymphoid system, VEGF expression was analysed in tissues, employing in situ hybridization with a 35S‐labelled RNA probe specific for this cytokine. Significant expression of VEGF transcripts was observed in Hodgkin's disease and peripheral T‐cell lymphomas, particularly of the angioimmunoblastic type. In contrast, expression of this cytokine was minimal or absent in follicle centre lymphoma and chronic lymphocytic leukemia of B‐cell type. VEGF was mainly observed in reactive non‐lymphoid CD68‐negative cells, which probably represent fibroblasts or myofibroblasts. In normal and ulcerated tonsils, VEGF was expressed in the squamous epithelium but only rarely found in the lymphoid tissue. Although infectious mononucleosis tonsils contained high numbers of VEGF‐positive cells in the interfollicular zone, expression of this cytokine was not found in Epstein–Barr virus (EBV)‐infected cells, as determined by simultaneous in situ hybridization for VEGF and EBV‐encoded small nuclear RNAs (EBER). In 5/8 cases of Castleman's disease, germinal centres containing small vessels also showed expression of VEGF, in contrast to normal tonsillar germinal centres which are devoid of both vessels and VEGF transcripts. It is concluded that VEGF may be involved in the induction of the angiogenesis of both peripheral T‐cell lymphomas and Hodgkin's disease, but not in low‐grade B‐cell lymphomas. In contradistinction to solid tumours, in which this cytokine is commonly secreted by the tumour cells themselves, in malignant lymphoma VEGF is not a product of neoplastic cells. Vascularization of germinal centres in Castleman's disease may also be a consequence of abnormal local expression of VEGF. © 1997 by John Wiley & Sons, Ltd.

Angiogenesis in myelodysplastic syndromes

“…The correlation between angiogenesis and progression to leukaemia is further supported by the observation that MDS patients with enhanced blasts accumulation and, in particular, the RAEB-t in addition to CMML and fibrosis subsets, show an increased MVD. Regarding the CMML and fibrosis MDS subsets, our finding of an increased MVD compared to RA, RARS and RAEB subsets correlates well with recent observations of VEGF generation by solid tumour-associated macrophages (Lewis et al, 1995) and fibroblasts (Foss et al, 1997;Fukumura et al, 1998). In fact, VEGF is currently considered the most relevant and the only endothelium-specific one among already known endothelial cell mitogenic factors, and it seems to be involved in the vascular phase of many different neoplastic diseases (Ferrara and Davis-Smyth, 1997).…”

“…More indirect evidence of neovascularization in leukaemia comes from the observation that vascular endothelial growth factor (VEGF) is expressed by acute myeloid leukaemia (AML) cells and leukaemic cell lines and possibly act as a paracrine growth factor in the development of myeloid leukaemia (Fiedler et al, 1997). Moreover, it has been proposed that angiogenesis and VEGF could play a cardinal role also in lymphoma (Foss et al, 1997;Salven et al, 1997) and myeloma (Vacca et al, 1994) development. We were interested in determining whether conversion of normal cells into preleukaemic-myelodysplastic (MDS), and ultimately leukaemic cells is a multistep process requiring the generation of new blood vessels.…”

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

“…VEGF peptide (VEGF [A-20]: sc-152 P; Santa Cruz Biotechnology) was used for VEGF neutralization. As positive human control tissues, tonsil, rheumatoid arthritis synovium, and colon tumor were used (30)(31)(32).…”

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

“…In non-Hodgkin's lymphomas, expression of angiogenic factors in cell lines (Bellamy et al, 1999) and tissue (Doussis-Anagnostopoulou et al, 1997;Foss et al, 1997;Turley et al, 1998) has been demonstrated.…”