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Previous Volume 331:1259-1264 November 10, 1994 Number 19 Next

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ABSTRACT

Background We have previously demonstrated a strong association between nuclear accumulation of p53 protein, as determined by immunohistochemical analysis, and mutations in the p53 gene. The purpose of this study was to determine the relation between nuclear accumulation of p53 and tumor progression in transitional-cell carcinoma of the bladder.

Methods Histologic specimens of transitional-cell carcinoma of the bladder (stages Pa, noninvasive disease, to P4, disease with direct extension into adjacent organs or structures) from 243 patients who were treated by radical cystectomy were examined for the immunohistochemical detection of p53 protein. Nuclear p53 reactivity was then analyzed in relation to time to recurrence and overall survival.

Results The detection of nuclear p53 was significantly associated with an increased risk of recurrence of bladder cancer (P<0.001) and with decreased overall survival (P<0.001). In patients with cancer confined to the bladder, the rates of recurrence for stage P1, P2, and P3a tumors that had no detectable nuclear p53 reactivity at five years were 7, 12, and 11 percent, respectively, as compared with 62, 56, and 80 percent, respectively, for tumors that had p53 immunoreactivity. Similar results were obtained when the presence or absence of p53 in the nuclei of the tumor cells was studied in relation to overall survival. In a multivariable analysis stratified according to grade, pathological stage, and lymph-node status, nuclear p53 status was an independent predictor (and in cancer confined to the bladder, the only independent predictor) of recurrence and overall survival (P<0.001).

Conclusions In patients with transitional-cell carcinoma confined to the bladder, an accumulation of p53 in the tumor-cell nuclei detected by immunohistochemical methods predicts a significantly increased risk of recurrence and death, independently of tumor grade, stage, and lymph-node status. Patients with transitional-cell carcinoma confined to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.

Source Information

From the Departments of Urology (D. Esrig, D. Elmajian, J.A.F., J.P.S., D.G.S., P.A.J.), Preventive Medicine (S.G., S.-C.C.), and Pathology (P.W.N., R.J.C.), University of Southern California School of Medicine and Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles.

Address reprint requests to Dr. Cote at the Department of Pathology, University of Southern California School of Medicine, Kenneth Norris Jr. Cancer Center, 1441 Eastlake Ave., Los Angeles, CA 90033.

Full Text of this Article

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p53 and Bladder Cancer
Li W. W., Li V. W., Tsakayannis D., Xing X., Wood L. L., Cote R. J., Skinner D. G., Jones P. A.
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