Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis.
Rao-JY; Hemstreet-GP III; Hurst-RE; Bonner-RB; Jones-PL; Min-KW; Fradet-Y
Proc Natl Acad Sci U.S.A. 1993 Sep; 90(17):8287-8291
A study of changes in phenotypic biochemical markers in the bladder epithelium during development of bladder cancer was conducted. Touch specimens were prepared from biopsy specimens obtained from tumors, adjacent bladder epithelium, and distal epithelium from 30 patients with transitional cell carcinoma (TCC) of the bladder and six urology patients without bladder cancer (controls). Individual bladder epithelial cells in the specimens were scored for DNA ploidy and expression of epidermal growth factor receptor (EGFR) and the oncogenic proteins G-actin, p185 and p300 by quantitative fluorescence image analysis techniques. The cells were also scored for suspicious morphology by a standard cytological procedure. With the exception of G-actin, a clear progression in the intensity of the various markers from the distant biopsy sites to the adjacent field of the tumor was seen in specimens from the TCC patients. Cluster analysis showed that the markers could be placed into three groups: G-actin and EGFR expression, DNA ploidy and p185 expression and cytology, and p300 expression. Expression of these markers in the controls was very low. Every tumor had significantly elevated expression of G-actin and 26 of 30 tumors were abnormal for p300. Cells with abnormal DNA ploidy were seen in 50% of the grade 1 tumors, 79% of the grade 2 tumors, and 88% of grade 3 tumors. High grade TCCs (graded 3 or higher) contained more EGFR and abnormal DNA ploidy and produced more p300 than low grade tumors. Ten to 60% of the biopsies obtained at sites distant from the tumors showed abnormal expression of at least one marker. The authors conclude that development of bladder cancer is accompanied by a sequence of phenotypic marker changes. These changes also occur at sites distant from the tumors. Changes in the expression of the markers may be useful for identifying high risk patients and monitoring the effects of treatment.
NIOSH-Publication; NIOSH-Grant; Cancer; Bladder-cancer; Clinical-diagnosis; Genetics; Fluorometry; Diagnostic-techniques; Humans
Urology University of Oklahoma Dept of Urology, PO Box 26901 Oklahoma City, OK 73190
Proceedings of the National Academy of Sciences of the United States of America
University of Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma