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Cellular F-Actin Levels as a Marker for Cellular Transformation: Correlation with Bladder Cancer Risk¹

Departments of Urology [J. Y. R., G. P. H., R. E. H., R. B. B., P. L. J.], Pathology [K. W. M., G. P. H.,] Biochemistry and Molecular Biology [R. E. H., P. L. J.], and Environmental Health Sciences [G. P. H., R. E. H.], University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190

Previous findings in cultured cells that differentiated cells had markedly higher F-actin levels than undifferentiated cells (Cancer Res., 50: 2215–2220, 1990) suggested that quantitative F-actin measurements in urinary cells might provide diagnostic or prognostic information by identifying those individuals with cells tending towards a lower degree of differentiation. The feasibility of such an approach was investigated using a risk stratification schema. Bladder wash samples were obtained from 163 symptomatic patients being evaluated for bladder cancer and 41 asymptomatic controls without hematuria or other symptoms consistent with bladder cancer. F-actin levels were evaluated by flow cytometry using a fluorescent phalloidin probe. The risk of bladder cancer was stratified according to biopsy, either DNA ploidy by flow cytometry or quantitative fluorescence image analysis cytology, previous bladder cancer history, and hematuria. A strong correlation between the presence of cells with abnormally low F-actin content in cells obtained by bladder wash from 38 patients and biopsy-proved bladder transitional cell carcinoma (P < 0.001) was observed. A strong correlation was also observed between the presence of cells with low F-actin content and risk of bladder cancer assessed by either stratification schema (P < 0.0001). The correlation was more consistent with the stratification by quantitative fluorescence image analysis cytology because of the 37% false-positive rate of ploidy analysis by flow cytometry among the control patients. Further evidence that low F-actin was correlated with cellular abnormality was obtained from simultaneously labeling cells for F-actin and with M344 antibody, a monoclonal antibody against a low-grade bladder tumor-related antigen. These studies showed that the F-actin content of the M344-positive cells was lower than that of the M344-negative cells. These results suggest that F-actin could be an early and sensitive marker for bladder cancer detection and risk prognostication.

¹ This work is the second in a series. It was supported, in part, by a subcontract from the Cancer Institute of the Chinese Academy of Medical Sciences, Beijing, P. R. C., for "Quantitative Fluorescence Image Analysis (QFIA) of Esophageal Samples to Detect Abnormal Levels of Nuclear Nucleic Acid," as a part of a National Cancer Institute-sponsored "Study of the Effect of Nutritional Intervention on Intermediate Endpoints of Esophageal Cancer in Linxian, China," and by a Postdoctoral Research Fellowship awarded to J. Y. R. by the Graduate College of the University of Oklahoma Health Sciences Center, and in part by the Veterans Administration and Centers for Disease Control/National Institute of Occupational Safety and Health Grant R01-OH02647.

² To whom requests for reprints should be addressed, at Department of Urology, Oklahoma University Health Sciences Center, P. O. Box 26901, Oklahoma City, OK 73190.

Received 8/28/90. Accepted 3/13/91.

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