Expression of VEGF and Its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer

Pradeep Kumar Kopparapu, Stephen A. Boorjian, Brian D. Robinson, Martin Downes, Lorraine J. Gudas, Nigel P. Mongan, Jenny L. Persson

Research output: Contribution to journalArticle

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Abstract

Aim: 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 nonmuscle 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. Materials and 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. Conclusion: Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.

Original languageEnglish (US)
Pages (from-to)2381-2390
Number of pages10
JournalAnticancer Research
Volume33
Issue number6
StatePublished - Jun 2013

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Vascular Endothelial Growth Factor Receptor
Urinary Bladder Neoplasms
Vascular Endothelial Growth Factor A
Muscle Neoplasms
Recurrence
Mucous Membrane
Messenger RNA
Survival
Neoplasms
Urinary Bladder
Proteins
Lymph Nodes
Databases
Neoplasm Metastasis
Muscles
Antibodies

Keywords

  • Angiogenesis
  • Bladder cancer
  • Disease recurrence
  • VEGF
  • VEGFR1
  • VEGFR2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kopparapu, P. K., Boorjian, S. A., Robinson, B. D., Downes, M., Gudas, L. J., Mongan, N. P., & Persson, J. L. (2013). Expression of VEGF and Its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. Anticancer Research, 33(6), 2381-2390.

Expression of VEGF and Its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. / Kopparapu, Pradeep Kumar; Boorjian, Stephen A.; Robinson, Brian D.; Downes, Martin; Gudas, Lorraine J.; Mongan, Nigel P.; Persson, Jenny L.

In: Anticancer Research, Vol. 33, No. 6, 06.2013, p. 2381-2390.

Research output: Contribution to journalArticle

Kopparapu, PK, Boorjian, SA, Robinson, BD, Downes, M, Gudas, LJ, Mongan, NP & Persson, JL 2013, 'Expression of VEGF and Its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer', Anticancer Research, vol. 33, no. 6, pp. 2381-2390.
Kopparapu PK, Boorjian SA, Robinson BD, Downes M, Gudas LJ, Mongan NP et al. Expression of VEGF and Its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. Anticancer Research. 2013 Jun;33(6):2381-2390.
Kopparapu, Pradeep Kumar ; Boorjian, Stephen A. ; Robinson, Brian D. ; Downes, Martin ; Gudas, Lorraine J. ; Mongan, Nigel P. ; Persson, Jenny L. / Expression of VEGF and Its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. In: Anticancer Research. 2013 ; Vol. 33, No. 6. pp. 2381-2390.
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abstract = "Aim: 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 nonmuscle 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. Materials and 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. Conclusion: Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.",
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AU - Kopparapu, Pradeep Kumar

AU - Boorjian, Stephen A.

AU - Robinson, Brian D.

AU - Downes, Martin

AU - Gudas, Lorraine J.

AU - Mongan, Nigel P.

AU - Persson, Jenny L.

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N2 - Aim: 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 nonmuscle 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. Materials and 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. Conclusion: Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.

AB - Aim: 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 nonmuscle 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. Materials and 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. Conclusion: Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.

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