Accumulation of nuclear p53 and tumor progression in bladder cancer

David Esrig, Donald Elmajian, Susan Groshen, John A. Freeman, John P. Stein, Su Chiu Chen, Peter W. Nichols, Donald G. Skinner, Peter A. Jones, Richard J Cote

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1259-1264
Number of pages6
JournalNew England Journal of Medicine
Volume331
Issue number19
DOIs
StatePublished - Nov 10 1994
Externally publishedYes

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Urinary Bladder Neoplasms
Urinary Bladder
Transitional Cell Carcinoma
Neoplasms
Recurrence
Survival
Cell Nucleus
Lymph Nodes
Cystectomy
p53 Genes
Clinical Protocols
Proteins
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Esrig, D., Elmajian, D., Groshen, S., Freeman, J. A., Stein, J. P., Chen, S. C., ... Cote, R. J. (1994). Accumulation of nuclear p53 and tumor progression in bladder cancer. New England Journal of Medicine, 331(19), 1259-1264. https://doi.org/10.1056/NEJM199411103311903

Accumulation of nuclear p53 and tumor progression in bladder cancer. / Esrig, David; Elmajian, Donald; Groshen, Susan; Freeman, John A.; Stein, John P.; Chen, Su Chiu; Nichols, Peter W.; Skinner, Donald G.; Jones, Peter A.; Cote, Richard J.

In: New England Journal of Medicine, Vol. 331, No. 19, 10.11.1994, p. 1259-1264.

Research output: Contribution to journalArticle

Esrig, D, Elmajian, D, Groshen, S, Freeman, JA, Stein, JP, Chen, SC, Nichols, PW, Skinner, DG, Jones, PA & Cote, RJ 1994, 'Accumulation of nuclear p53 and tumor progression in bladder cancer', New England Journal of Medicine, vol. 331, no. 19, pp. 1259-1264. https://doi.org/10.1056/NEJM199411103311903
Esrig D, Elmajian D, Groshen S, Freeman JA, Stein JP, Chen SC et al. Accumulation of nuclear p53 and tumor progression in bladder cancer. New England Journal of Medicine. 1994 Nov 10;331(19):1259-1264. https://doi.org/10.1056/NEJM199411103311903
Esrig, David ; Elmajian, Donald ; Groshen, Susan ; Freeman, John A. ; Stein, John P. ; Chen, Su Chiu ; Nichols, Peter W. ; Skinner, Donald G. ; Jones, Peter A. ; Cote, Richard J. / Accumulation of nuclear p53 and tumor progression in bladder cancer. In: New England Journal of Medicine. 1994 ; Vol. 331, No. 19. pp. 1259-1264.
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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.",
author = "David Esrig and Donald Elmajian and Susan Groshen and Freeman, {John A.} and Stein, {John P.} and Chen, {Su Chiu} and Nichols, {Peter W.} and Skinner, {Donald G.} and Jones, {Peter A.} and Cote, {Richard J}",
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AU - Esrig, David

AU - Elmajian, Donald

AU - Groshen, Susan

AU - Freeman, John A.

AU - Stein, John P.

AU - Chen, Su Chiu

AU - Nichols, Peter W.

AU - Skinner, Donald G.

AU - Jones, Peter A.

AU - Cote, Richard J

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N2 - 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.

AB - 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.

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