title: The expression of osteopontin and vascular endothelial growth factor in correlation with angiogenesis in monoclonal gammopathy of undetermined significance and multiple myeloma.
abstract: Several studies have shown a gradual increase in the extent of bone marrow angiogenesis in various stages of proliferative plasma cell disorders, from monoclonal gammopathy of undetermined significance (MGUS) to active multiple myeloma (MM). The main aim of this study was to evaluate tumor angiogenesis parameters in detail and to correlate them with the expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in the bone marrow of patients with MGUS and MM. In addition, we wanted to determine their prognostic significance in active MM. Ninety-five patients were enrolled in the study: 14 diagnosed with MGUS, 13 with asymptomatic myeloma (AMM) and 68 with active MM. Computer assisted image analysis was used to determine the angiogenesis parameters, the quantity of microvessels per 1mm(2) (MVD), the area occupied by microvessels per 1mm(2) and the percentage of microvessel area in total section area (TVA). Double immunohistochemical methods CD138+VEGF and CD138+OPN were used to evaluate expression of these proteins in plasma cells, and OPN was also analyzed for its interstitial expression (iOPN). A significant positive correlation was determined between VEGF and iOPN with angiogenic parameters in the MGUS stage of the disease. In advanced stages of the disease, a significant negative correlation was recorded between OPN and iOPN with parameters of angiogenesis. Overall survival was significantly shorter for patients with negative iOPN (p=0.002) and higher angiogenic parameters, MVD (p=0.009), TVA (p=0.008) and area of microvessels per 1mm(2) (p=0.02). Positive VEGF expression in our model predicted a better three-year survival of patients with active MM (OR: 5.25, p=0.03; HR: 0.44, p=0.04). The results of our study suggested a possible key role of VEGF and OPN in the induction of angiogenesis in early-stage disease.
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia. Electronic address: esinozic@gmail.com.
authors.forename: Emina
authors.initials: E
authors.lastname: Babarović
authors.affiliation: Department of Hematology, Rijeka University Hospital Center, Krešimirova 42, 51000 Rijeka, Croatia.
authors.forename: Toni
authors.initials: T
authors.lastname: Valković
authors.affiliation: Department of Hematology, Rijeka University Hospital Center, Krešimirova 42, 51000 Rijeka, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Budisavljević
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Balen
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Štifter
authors.affiliation: Department of Hematology, Rijeka University Hospital Center, Krešimirova 42, 51000 Rijeka, Croatia.
authors.forename: Antica
authors.initials: A
authors.lastname: Duletić-Načinović
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Lučin
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Nives
authors.initials: N
authors.lastname: Jonjić
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009101:Multiple Myeloma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin
keywords: Angiogenesis; Monoclonal gammopathy of undetermined significance; Multiple myeloma; Osteopontin; Vascular endothelial growth factor