title: Increased expression of vascular endothelial growth factor receptor 1 correlates with VEGF and microvessel density in Philadelphia chromosome-negative myeloproliferative neoplasms.
abstract: OBJECTIVE
  The authors investigated vascular endothelial growth factor receptor 1 (VEGFR-1) protein expression in a series of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs) and its correlations with microvessel density (MVD) and vascular endothelial growth factor (VEGF).
  
  
  METHODS
  83 bone marrow biopsies of Ph- MPNs patients, including 27 essential thrombocythaemia (ET), 21 polycythaemia vera (PV) and 35 primary myelofibrosis (PMF), and 10 normal controls (NCs) were investigated by immunohistochemistry.
  
  
  RESULTS
  Patients with PV and PMF showed an increased MVD (PV: 20.1±10.6; PMF: 25.8±6.5) compared with those with ET or NCs (ET: 10.4±4.6; NCs: 7±3.4). VEGFR-1 expression was increased in Ph- MPNs, particularly in PV and PMF (NCs: 0.07±0.03; ET: 0.15±0.09; PV: 0.31±0.2; PMF: 0.31±0.04). VEGF expression parallelled VEGFR-1 and resulted increased in Ph- MPNs (NCs: 0.08±0.04; ET: 0.13±0.06; PV: 0.29±0.2; PMF: 0.31±0.15) and higher in post-polycythaemic myelofibrosis and in the fibrotic stage of PMF than in the non-fibrotic phases of both diseases. VEGFR-1 protein expression correlated with MVD and VEGF expression in Ph- MPNs. VEGFR-1 and VEGF were expressed by the same bone marrow populations: megakaryocytes, macrophages and immature myeloid precursors showed a moderate to strong immunostaining intensity in both Ph- MPNs and NCs. The erythroid precursors were not immunoreactive.
  
  
  CONCLUSIONS
  VEGFR-1 and VEGF were increased and co-localised in megakaryocytes, macrophages and myeloid precursors of Ph- MPNs. This finding supports the hypothesis of a VEGF/VEGFR-1 autocrine loop in the neoplastic cells of Ph- MPNs.
authors.affiliation: Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Milan Medical School, A.O. San Paolo, and Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Boiocchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Vener
authors.forename: Federica
authors.initials: F
authors.lastname: Savi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bonoldi
authors.forename: Alessia
authors.initials: A
authors.lastname: Moro
authors.forename: Nicola Stefano
authors.initials: NS
authors.lastname: Fracchiolla
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.forename: Giorgio Lambertenghi
authors.initials: GL
authors.lastname: Deliliers
authors.forename: Guido
authors.initials: G
authors.lastname: Coggi
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010677:Philadelphia Chromosome; D011087:Polycythemia Vera / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1