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The Angiogenic Factor Midkine Is Expressed in Bladder Cancer, and Overexpression Correlates with a Poor Outcome in Patients with Invasive Cancers¹

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

Midkine (MK) is a member of a family of heparin-binding growth factors, which are reported to be angiogenic. We have investigated by RNase protection analysis the expression of MK in 47 primary bladder tumors and 7 normal bladder samples.

MK mRNA transcripts were detectable in 46 (98%) of 47 of the tumors and in 5 (70%) of 7 of the normal bladder samples. However, median MK expression was 4-fold higher in tumors than in the normal bladder (P < 0.004). In eight tumors (17%), MK expression was elevated more than 10-fold compared with the median value of the normal bladder specimens. There was no statistically significant difference in expression between superficial and invasive tumors (P < 0.50).

Seven (32%) of 22 patients with invasive cancers are alive at 1 year with no evidence of recurrence; in 5 (70%) of these patients, MK expression in the tumor was within the normal range at the time of presentation. By contrast, in only 2 (13%) of 15 patients who died or whose tumors recurred or progressed was MK expression in the normal range (P < 0.01). Overall, median MK expression in invasive tumors that caused death, progressed, or recurred within 12 months was 3-fold higher than that found in the tumors of those patients who were clear of disease at 12 months (P < 0.04).

Thus, overexpression of MK is associated with the development of bladder cancer and in invasive cancers predicts a poor clinical outcome in the short term.

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, at Imperial Cancer Research Fund, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.

Received 3/ 4/96. Accepted 4/17/96.

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