title: Angiogenesis in upper tract urothelial carcinoma associated with Balkan endemic nephropathy.
abstract: Upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN) is characterized by a number of aberrations in cell-cycle regulation and apoptosis. The aim of this study was to detect angiogenesis-related marker(s) specific for BEN UTUC, and to examine the influence of HIF 1α upon angiogenesis and apoptosis in UTUC. Present investigation included 110 patients with UTUC, 50 from BEN region and 60 control tumors. Altered expression of VEGFR1 was more often present in control UTUC than in BEN tumors (p<0.005). It was associated with high grade, low and high stage, solid growth, and metaplastic change of control UTUC. Microvessel density assessed by CD31 (MVD CD31) was significantly higher in UTUC with lymphovascular invasion (p<0.05), and in BEN tumors with papillary growth (p<0.05). Discriminant analysis indicated that BEN and control tumors do not differ significantly in expression of angiogenesis related markers. The most important discriminant variable that determined control UTUC was expression of VEGFR1 (p=0.002). HIF 1α in UTUC significantly correlated with the low stage, papillary growth and expression of Bcl-2, Caspase-3 index, and MVD CD34 (p<0.001; 0.0005; 0.01; 0.005; 0.01, respectively). HIF-1α may be helpful marker in evaluation of UTUC, especially when combined with angiogenesis and apoptosis.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Nis, Nis, Serbia.
authors.forename: Ljubinka
authors.initials: L
authors.lastname: Jankovic Velickovic
authors.forename: Ana
authors.initials: A
authors.lastname: Ristic Petrovic
authors.forename: Slavica
authors.initials: S
authors.lastname: Stojnev
authors.forename: Zana
authors.initials: Z
authors.lastname: Dolicanin
authors.forename: Takanori
authors.initials: T
authors.lastname: Hattori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugihara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Mukaisho
authors.forename: Mariola
authors.initials: M
authors.lastname: Stojanovic
authors.forename: Vladisav
authors.initials: V
authors.lastname: Stefanovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001449:Balkan Nephropathy / Q000175:diagnosis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007682:Kidney Pelvis / Q000473:pathology*; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D009392:Nephrectomy; D014513:Ureter / Q000098:blood supply / Q000601:surgery; D014516:Ureteral Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D040281:Vascular Endothelial Growth Factor Receptor-1