Prognostic evaluation of the microvascular network in myelodysplastic syndromes

Abstract

Considering the recently stated suggestion of neovascularization being implicated in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple morphometric microvascular characteristics in MDS, in relation to clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS patients were immunostained for factor VIII and compared to those from 20 controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia (AML) patients. Quantitation of microvessel density (MVD), area, total vascular area (TVA), major and minor axis length, perimeter, compactness, shape factor, Feret diameter, and the number of branching vessels was performed by image analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis and shape factor values and significantly lower compactness than the control group. AML was characterized by increased vascularity compared to MDS and CMML, as well as by the presence of flattened microvessels (lower values of shape factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber vessels than RAEB, which explains the favorable prognostic effect of increased size-related parameters on progression and/or survival. Moreover, decreased compactness and MVD were independent predictors of longer progression-free survival. It is concluded that angiogenesis is involved in the conversion of normal marrow to MDS and ultimately to AML and that disease progression within MDS is accompanied by qualitative alterations of the microvascular network. Furthermore, size-related parameters affect survival, while shape-related parameters and MVD are more influential with regard to progression-free survival. Leukemia (2001Leukemia ( ) 15, 1369Leukemia ( -1376

Angiogenesis in Hodgkin's lymphoma: a morphometric approach in 286 patients with prognostic implications

“…The permissive role of the low values of shape factor in terms of disease progression has also been recorded in myelodysplastic syndromes. 11 In summary, the present study provides evidence that the maximum level of microvessel formation coincides with the early stages of HL and that progression in stage is accompanied by qualitative, rather than quantitative, alterations in microvascular network. More importantly, the assessment of microvascular network provides independent prognostic information in HL, requiring the concomitant evaluation of the vascular density and the size and shape of the microvessels.…”

“…8,11 Briefly, immunohistochemically stained slides for CD34 were scanned, field per field, at  100 magnification, to identify the region showing the most intense vascularization ('hot spot') 7,25 ( Figure 1). In cases including remnants of normal tissue (eg interfollicular HL), these areas were shielded to ensure that microvessel counting was performed in neoplastic tissue.…”

“…5 A plethora of investigations support the intuitive notion that solid tumors progress in concert with an induction of neovascular response (for a review see Hlatky et al 6 ). Evidence of the importance of angiogenesis in hematologic malignancies is rapidly accruing, indirectly implicating bone marrow angiogenesis in the pathophysiology and course of acute leukemias, 7 chronic myeloid and lymphoid leukemias, [8][9][10] myelodysplastic syndromes 11 and multiple myeloma. 12,13 In non-Hodgkin's lymphomas (NHL) and B chronic lymphocytic leukemia, microvessel counts correlate with histologic grade and clinical stage, respectively.…”

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

“…4 In addition to the well-established role of angiogenesis in solid tumors, 4 the increase in tumor vascularity has been previously investigated in a variety of hematological neoplasms, including acute lymphatic 15 and myeloid 16,17 leukemias, myelodysplastic syndromes, 14,18 Hodgkin's disease, 19 myeloma, 20-25 lymphoproliferative disorders, 26-31 systemic mastocytosis 32 and chronic myeloproliferative disorders, 5,14 including CIMF. 8 The number of small vessels in a tumor, or MVD, is considered a surrogate indicator of angiogenesis.…”

Does CD34 Staining Reflect the Angiogenic Process in the Bone Marrow? An Analysis of a Series of Chronic Myeloid Leukemia Patients

“…The close interdependence between the bone marrow vessels and the hematopoietic cells has long been appreciated. Recent interest in bone marrow vascularity has brought to light the production of hematopoietic growth factors by endothelial cells [8,9]. These capillaries and sinusoids are functionally dormant and non-patent in a normal marrow which accounts for sparse MVD in a normal marrow.…”