title: Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) signaling is frequently altered in invasive tumor cells and is associated with patient outcome. In the present study, we examined VEGF, VEGFR1, and VEGFR2 expression in non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), and evaluated the association between VEGF and its receptors with disease characteristics and bladder cancer recurrence.
  
  
  METHODS
  Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder mucosa (n=131) were immunostained using antibodies against VEGF, VEGFR1, and VEGFR2. The association between the expression of these proteins and clinical parameters including stage, lymph node metastasis, and recurrence-free survival were statistically evaluated. VEGF mRNA expression data were extracted from the public Oncomine database.
  
  
  RESULTS
  VEGF and VEGFR1 mRNA levels were significantly higher in bladder cancer specimens than that of normal mucosa (for VEGF, p<0.001; for VEGFR1, p=0.02). Analysis of their expression at protein levels showed that levels of VEGF and VEGFR1 were significantly higher in NMIBC than in MIBC (p<0.001), while that of VEGFR2 was significantly higher in all cancer specimens compared to benign urothelial mucosa (p=0.001). Further-more, the expression of VEGFR2 was significantly higher in MIBC, as compared to NMIBC (p<0.001). Patients with higher levels of VEGF, VEGFR1, and VEGFR2 tended to have poorer recurrence-free survival than those with lower levels, but this was not statistically significant.
  
  
  CONCLUSIONS
  Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.
authors.affiliation: Section for Experimental Cancer Research, Department of Laboratory Medicine in Malmö, Lund University, Clinical Research Center, 205 02 Malmö, Sweden.
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Kopparapu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.forename: Martin
authors.initials: M
authors.lastname: Downes
authors.forename: Lorraine J
authors.initials: LJ
authors.lastname: Gudas
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Mongan
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Persson
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: VEGF; VEGFR1; VEGFR2; angiogenesis; bladder cancer; disease recurrence