B-cell non-Hodgkin's lymphomas express heterogeneous patterns of neovascularization

Abstract

BACKGROUND AND OBJECTIVES: The role of angiogenesis in the growth and survival of hematologic malignancies was not clear until recently. We have previously demonstrated in beta-cell non Hodgkin's lymphomas (B-NHL), that neoplastic progression, as defined by its increasing malignancy grades, is clearly related to the degree of angiogenesis. DESIGN AND METHODS: In the present study we used transmission electron microscopy to examine the ultrastructural patterns of neovascularization in both low and high grade B-NHL). In low grade B-NHL the vessel lumen was formed either by endothelial cell body curving or, more frequently, by the fusion of intracellular vacuoles in poorly differentiated endothelial cells. In high grade B-NHL, on the other hand, the predominant neo-angiogenic pattern was the formation of a slit-like lumen. A remarkable ultrastructural feature in high-grade B-NHL was the intimate relationship between endothelial and tumor cells. Both low and high grade B-NHL exhibited development of transluminal bridges in larger vessels, leading to the division of the vessel. INTERPRETATION AND CONCLUSIONS: These in situ data suggest that the intrinsic process of endothelial cell proliferation and vessel formation in the stroma of B-NHL varies according to the grade of tumor malignancy and point to the important role played by the specific organ microenvironment, which determines the extent of cancer cell proliferation, angiogenesis and invasion. In fact, the microenvironment has an important influence on vascular architecture, i.e., the properties of tumor cells can also determine the outcome of the angiogenic response. Taken together our findings, which provide quantitative data on different vascular patterns in B-NHL, have potential implications for vascular targeting and cancer therapy.