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Different Angiogenic Pathways Characterize Superficial and Invasive Bladder Cancer¹

Molecular Angiogenesis Group, Imperial Cancer Research Fund, Institute of Molecular Medicine [T. O., R. B., A. L. H.], and Nuffield Department of Surgery [T. O., S. F.], University of Oxford, Oxford, OX3 9DU, and Department of Urology, Churchill Hospital, Oxford, OX3 7DL [T. O., D. C.], England

We have investigated by RNase protection analysis the expression of 2 angiogenic factors in 45 primary bladder tumors and 8 normal bladders.

Expression of vascular endothelial growth factor (VEGF) was 3-fold higher and that of platelet-derived endothelial cell growth factor was 40-fold higher in tumors compared to normal bladder. However, the factors were differentially expressed in different stages of the cancer. Expression of VEGF in superficial tumors was 4-fold higher than in invasive tumors and 10-fold higher than in normal bladder (superficial versus invasive, P < 0.0006; superficial versus normal, P < 0.0002). Expression of platelet-derived endothelial cell growth factor in invasive tumors was 33-fold higher than in superficial tumors and 260-fold higher than in normal bladder (invasive versus superficial, P < 0.0001; invasive versus normal, P < 0.0003).

In well differentiated or moderately differentiated superficial tumors which had invaded the lamina propria (pT1G1/2) VEGF expression was 4-fold higher in tumors which subsequently recurred at 3 months compared to those which did not recur (P < 0.002).

Thus there are two distinct angiogenic pathways involved in different stages of bladder cancer, which is in keeping with the evidence for two different genetic pathways. Elevated VEGF expression predicts early recurrence of pT1G1/2 tumors.

¹ T. O. was supported by The Private Patients Plan Research Scholarship of the Royal College of Surgeons of England. S. F. is supported by the Medical Research Council. R. B. and A. H. are supported by The Imperial Cancer Research Fund.

² To whom requests for reprints should be addressed.

Received 12/13/94. Accepted 12/28/94.

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