Published in Cancer Detection and Prevention 1999; 23(2):163-171.

Biomarkers in Monitoring for Efficacy of Immunotherapy and Chemoprevention of Bladder Cancer with Dimethylsulfoxide

George P. Hemstreet III, M.D., Ph.D.,a,b,c,d Jian Yu Rao, M.D.,a Robert E. Hurst, Ph.D.,a,d,e Rebecca B. Bonner, M.S.,a John E. Mellott, B.S.,a and Gina M. Rooker, M.D.a

Departments of a Urology, b Pathology, c Microbiology and Immunology, d Occupational and Environmental Health, and eBiochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Address all correspondence and reprint requests to: George P. Hemstreet Ill, MD PhD, Department of Urology. University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190.

ABSTRACT: This study correlated biomarkers expressed in tumor and epithelial field with clinical response and recurrence. Of 25 bladder cancer patients, 11 received 6 weeks of intravesical Bacille Calmette-Guerin (BCG), and 14 were treated weekly with intravesical dimethylsulfoxide (DMSO) for 4 weeks to further modulate biomarker expression. G-actin, DNA aneuploidy, and p300 tumor antigen were evaluated by quantitative fluorescence image analysis on uroepithelial cells from bladder wash samples prior to and immediately following treatment. Excluding patients who did not respond to BCG (and who had persistently abnormal p300 and DNA markers), recurrence correlated with persistent abnormal G-actin findings. Of patients who were G-actin negative following therapy, only 25% recurred during follow-up in contrast to 67% in patients who were positive (p < 0.03 by Fisher's exact test). The odds ratio for recurrence was 6.00 (95% confidence interval: 1.3-28.6). Cytosolic G-actin levels can be an important intermediate end point marker for chemoprevention.

KEY WORDS: prognosis, recurrence, urine cells, uroepithelial cells.