title: A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations.
abstract: Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-alpha (IFN-alpha). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-alpha induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-alpha treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.
authors.affiliation: Department of Pathology, First Department of Internal Medicine, School of Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece. pkorko@cc.uoa.gr
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Despina A
authors.initials: DA
authors.lastname: Gribabis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Maria K
authors.initials: MK
authors.lastname: Angelopoulou
authors.forename: Marina P
authors.initials: MP
authors.lastname: Siakantaris
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Athina
authors.initials: A
authors.lastname: Androulaki
authors.forename: Irene
authors.initials: I
authors.lastname: Thymara
authors.forename: Styliani I
authors.initials: SI
authors.lastname: Kokoris
authors.forename: Maria C
authors.initials: MC
authors.lastname: Kyrtsonis
authors.forename: Christos
authors.initials: C
authors.lastname: Kittas
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000098:blood supply*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins