title: Combined Angiogenesis and Proliferation Markers' Expressions as Long-Term Prognostic Factors in Renal Cell Cancer.
abstract: The aim of this study was to evaluate the expression of MIB-1, BCL-2, VEGFR3, and CD31 and their associations with long-term survival in patients with renal cell cancer (RCC).
  
  
  
  This study consisted of 224 RCC patients who underwent radical nephrectomy from 1985 to 1995. Follow-up continued for up to over 20 years. MIB-1 and BCL-2 expression were analyzed alone, and additionally, the expression of MIB-1, BCL-2, VEGFR3, and CD31 were combined in pairs using the following groups: low/low, low/high, high/low, and high/high.
  
  
  
  Low BCL-2 expression (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.42-3.31; P < .001 compared with high BCL-2 in univariate analysis) and high MIB-1 expression (HR, 2.05; 95% CI, 1.32-3.19; P = .001 in multivariate analysis) were found to associate for poorer survival in RCC. In multivariate analysis, the combination of high MIB-1/low BCL-2 was associated with poor survival compared with low MIB-1/high BCL-2 (HR, 3.20; 95% CI, 1.66-6.17; P = .001), and the combination of low VEGFR3/high CD31 was associated with poor survival (HR, 2.48; 95% CI, 1.29-4.78; P = .007) compared with high VEGFR3/high CD31.
  
  
  
  Compared with high BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression, low BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression has poorer survival in the long-term follow-up of patients with RCC. Analysis of MIB-1, BCL-2, VEGFR3, and CD31 expression might be a useful additional marker to tailor the follow-up of RCC patients.
authors.affiliation: University of Tampere, School of Medicine, Tampere, Finland; Department of Anesthesia, Tampere University Hospital, Tampere, Finland. Electronic address: Virman.juha.p@student.uta.fi.
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: University of Tampere, School of Medicine, Tampere, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland.
authors.forename: Pirkko-Liisa I
authors.initials: PL
authors.lastname: Kellokumpu-Lehtinen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016019:Survival Analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; 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: BCL-2; CD31; MIB-1; RCC; VEGFR3