Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer.
Tumor development is angiogenesis dependent, and vascular endothelial growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficial bladder cancers was associated with earlier recurrence (P = 0.001; hazard ratio, 3.09) and progression to a more invasive phenotype (P = 0.02; hazard ratio, 5.33). VEGF mRNA expression correlated with protein levels in superficial tumors (r = 0.59, P = 0.003) and normal bladder (r = 0.65, P < 0.05), although the ratio of VEGF protein to mRNA was elevated in tumors compared to normal bladder (P = 0.004), suggesting posttranscriptional regulation. In this study, VEGF is implicated as a major downstream mediator of the effects of the p53 tumor suppressor gene by the association between high p53 protein (determined immunochemically) and high VEGF protein and mRNA expression (P < 0.02), although in cases without high p53 protein expression, high VEGF mRNA also predicts a poor prognosis. The relationship between VEGF and early tumor recurrence suggests that seeding via angiogenesis may be a major mechanism in the pathogenesis of recurrence. These studies indicate that VEGF can predict the behavior of superficial bladder tumors and is a therapeutic target for intravesical therapy.
Crew
J P
JP
Molecular Angiogenesis Group, Imperial Cancer Research Fund, The Institute of Molecular Medicine, University of Oxford, United Kingdom.
O'Brien
T
T
Bradburn
M
M
Fuggle
S
S
Bicknell
R
R
Cranston
D
D
Harris
A L
AL
D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D018450:Disease Progression; D018572:Disease-Free Survival; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D008222:Lymphokines / Q000032:analysis* / Q000096:biosynthesis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D012008:Recurrence; D012016:Reference Values; D015996:Survival Rate; D013997:Time Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D001743:Urinary Bladder / Q000166:cytology / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors