Published in Cancer Detection and Prevention 1996; 20(5).
Cytoskeletal actin as a intermediate end point marker for bladder cancer management1Dept Pathology and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90024; 2Dept Urology, University Oklahoma, Oklahoma City, OK 73190, USA
BACKGROUND: Actin changes may be a common feature in genetic and epigenetic carcinogenic mechanisms. Our previous studies showed the cytoskeletal G- and F-actin reflect differentiation-related changes in cells undergoing tumorigenesis and in adjacent "field" cells, and a pattern of low F-actin and high G-actin is indicative of increased risk (PNAS 1993; 90: 8287, Cancer Res 1991; 51: 2762,). In a group of over 1600 workers exposed to carcinogen benzedine, G-actin correlated with exposure, establishing it as an marker of effect. AIM: To study actin as a marker to modulate bladder cancer prevention and treatment. METHODS: A profile of biomarkers was monitored in a series of twenty-six patients undergoing transurethral resection, receiving BCG (12 patients) and DMSO (14 patients). G-actin, DNA aneuploidy and p300 were monitored weekly by Quantitative Fluorescence Image Analysis on uroepithelial cells from bladder wash samples. RESULTS: BCG normalized DNA ploidy in 89% of the cases and p300 in 68% of cases (P<0.001 and P<0.02, respectively), but not G-actin, the early differentiation marker. In contrast, the cell differentiation agent, DMSO, normalized G-actin in 70% of cases treated (P<0.05) but not the later-occurring tumor specific markers, DNA and p300. Excluding patients who did not respond to BCG, recurrence correlated with persistent biochemical field disease as defined by abnormal G-actin. These findings strongly support the hypothesis that G-actin levels can be an important intermediate endpoint marker for chemoprevention.
Paper presented at the International Symposium on the Impact of Cancer Biotechnology on Diagnostic and Prognostic Indicators; Nice, France; October 26 - 28, 1996; in the section on Prostate.