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[Cancer Research 61, 8659-8663, December 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Aberrant Promoter Methylation Profile of Bladder Cancer and Its Relationship to Clinicopathological Features1

Riichiroh Maruyama, Shinichi Toyooka, Kiyomi O. Toyooka, Kenichi Harada, Arvind K. Virmani, Sabine Zöchbauer-Müller, Alfredo J. Farinas, Funda Vakar-Lopez, John D. Minna, Arthur Sagalowsky, Bogdan Czerniak and Adi F. Gazdar2

Hamon Center for Therapeutic Oncology Research [R. M., S. T., K. O. T., K. H., A. K. V., S. Z-M., A. J. F., J. D. M., A. F. G.], and Departments of Pathology [A. K. V., A. F. G.], Internal Medicine [J. D. M.], Pharmacology [J. D. M.], and Urology [A. S.], University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, and Department of Pathology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030 [F. V-L., B. C.]

We investigated the aberrant promoter methylation profile of bladder cancers and correlated the data with clinicopathological findings. The methylation status of 10 genes was determined in 98 surgically resected bladder cancers, and we calculated the median methylation index (MI), a reflection of the methylated fraction of the genes tested. Methylation frequencies of the genes tested in bladder cancers were 36% for CDH1, 35% for RASSF1A and APC, 29% for CDH13, 16% for FHIT, 15% for RARß, 11% for GSTP1, 7% for p16INK4A, 4% for DAPK, and 2% for MGMT. Methylation of four of the individual genes (CDH1, RASSF1A, APC, and CDH13) and the MI were significantly correlated with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern). Methylation of CDH1, FHIT, and a high MI were associated with shortened survival. CDH1 methylation positive status was independently associated with poor survival in multivariate analyses. Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in bladder cancer.




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