title: Novel Angiogenesis Markers as Long-Term Prognostic Factors in Patients With Renal Cell Cancer.
abstract: To evaluate Ang-2 expression alone and in combination with expression of cell proliferation and cell survival markers (MIB-1 and Bcl-2) and angiogenesis markers (VEGFR3 and CD31), and the associations of these markers with renal cell cancer (RCC) in long-term survival.
  
  
  
  Our study included 224 patients with RCC who were treated before the availability of antiangiogenic agents between 1985 and 1995, at the Pirkanmaa Hospital District in Finland. All tumor samples were reclassified and reevaluated by an experienced uropathologist, and parallel tissue microarrays (TMA) were performed for immunohistochemical analysis. Kaplan-Meier's survival estimation method and Cox proportional hazards models were used for survival analysis.
  
  
  
  The percentage of Ang-2 expression in the tumor area varied from 0.07 to 25.65. Ang-2 expression was significantly associated with the tumor grade and stage, as well as the MIB-1, Bcl-2, and VEGFR3 expression (P = .042, P = .019, P = .039, P = .013, and P = .005, respectively). The highest Ang-2 expression predicted better survival, P < .05. High Bcl-2 and low MIB-1 expression combined with Ang-2 expression was associated with better survival. Multivariate analysis showed poorer survival in patients with low Ang-2 or high MIB-1 expressions: HR 1.89, 95% CI 1.16 to 3.08, P = .010 and HR 2.20, 95% CI 1.36 to 3.54, P = .001, respectively.
  
  
  
  Very high Ang-2 expression was associated with better survival in patients with RCC. Ang-2 expression correlated with tumor stage and grade, but it was still an independent prognostic factor in a multivariate analysis.
authors.affiliation: Translational Cancer Biology Program, Research Program's Unit and Department of Virology, University of Helsinki and Wihuri Research Institute, Helsinki, Finland.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Lampinen
authors.affiliation: University of Tampere, School of Medicine, Tampere, Finland; Department of Anesthesia, Tampere University Hospital, Tampere, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Virman
authors.affiliation: Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.affiliation: Science Center, Pirkanmaa Hospital District and School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Tiina H
authors.initials: TH
authors.lastname: Luukkaala
authors.affiliation: Department of Oncology, Tampere University Hospital, Tampere, Finland.
authors.forename: Kaisa L
authors.initials: KL
authors.lastname: Sunela
authors.affiliation: Department of Pathology, Tampere University Hospital, Fimlab Laboratories, Tampere, Finland.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Kujala
authors.affiliation: Translational Cancer Biology Program, Research Program's Unit and Department of Virology, University of Helsinki and Wihuri Research Institute, Helsinki, Finland.
authors.forename: Pipsa
authors.initials: P
authors.lastname: Saharinen
authors.affiliation: University of Tampere, School of Medicine, Tampere, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland. Electronic address: klpike@uta.fi.
authors.forename: Pirkko-Liisa I
authors.initials: PI
authors.lastname: Kellokumpu-Lehtinen
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; C000595707:BCL2 protein, human; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019253:Proto-Oncogene Proteins c-bcl-2; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Angiogenesis; Angiopoietin-2 (Ang-2); Prognostic factors; Proliferation markers; Renal cell cancer (RCC)