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Can p53 staining be used to identify patients with aggressive superficial bladder cancer?

Can p53 staining be used to identify patients with aggressive superficial bladder cancer?
Can p53 staining be used to identify patients with aggressive superficial bladder cancer?

Approximately 10% of patients with superficial bladder cancer (pTa/pT1) recur with life-threatening muscle-invasive disease. Identification of these patients has been a major goal of bladder cancer research. In 1994, it was suggested that p53 immunostaining could identify the cancers that would progress and it was proposed that tumours that stain for p53 should be treated aggressively with radiotherapy or cystectomy. Despite the hundreds of studies published since on the relationship between p53 and progression in superficial bladder cancer, the clinical utility of p53 immunostaining has not been resolved because of limitations concerning the numbers of patients and the length of follow-up. This study set out to overcome these limitations by using tissue from a large multicentre trial that recruited 502 patients with a median follow-up of 10 years. Each of 34 patients that had progressed with >/= pT2 disease or had distant metastases or had died from bladder cancer was compared with one or two matched controls. Sections were stained with a mouse monoclonal antibody to p53, pAb1801. In agreement with many of the earlier studies, p53 immunostaining had prognostic significance. The adjusted hazard ratio for time to progression for the pAb1801-positive versus negative group was 2.5, with 95% confidence intervals of 1.05-5.98 (p = 0.039). The other major risk factor that is associated with progression of superficial bladder cancer is pT1G3 disease. Of the 42 pT1G3 cancers, 14 (33%) progressed. The proportion of cancers with p53 staining that progressed was similar to the proportion of pT1G3 cancers that progressed, but neither the sensitivity nor the specificity of association of p53 staining with progression is sufficient to recommend cystectomy in individual patients.

Antibodies, Monoclonal, Disease Progression, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Proteins, Risk Factors, Time Factors, Tumor Suppressor Protein p53, Urinary Bladder Neoplasms, Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
0022-3417
74-81
Masters, John R.W.
8ecf372e-6bd8-46ac-945c-7dc9568365e5
Vani, Urvi D.
eb357508-0dbf-4ef7-81c1-239f121a8368
Grigor, Kenneth M.
1c901a3c-7f5b-49fd-8c4d-52d5800ab79b
Griffiths, Gareth O.
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Crook, Angela
936ee817-1387-4d25-9623-197b96971805
Parmar, Mahesh K.B.
44634dd0-3f2b-4263-9f16-308a9e9260b8
Knowles, Margaret A.
d1b56591-53d1-41a1-80ce-96eb1e647fcd
MRC Superficial Bladder Cancer Group Mitomycin-C Trial Collaborators
Masters, John R.W.
8ecf372e-6bd8-46ac-945c-7dc9568365e5
Vani, Urvi D.
eb357508-0dbf-4ef7-81c1-239f121a8368
Grigor, Kenneth M.
1c901a3c-7f5b-49fd-8c4d-52d5800ab79b
Griffiths, Gareth O.
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Crook, Angela
936ee817-1387-4d25-9623-197b96971805
Parmar, Mahesh K.B.
44634dd0-3f2b-4263-9f16-308a9e9260b8
Knowles, Margaret A.
d1b56591-53d1-41a1-80ce-96eb1e647fcd

Masters, John R.W., Vani, Urvi D., Grigor, Kenneth M., Griffiths, Gareth O., Crook, Angela, Parmar, Mahesh K.B. and Knowles, Margaret A. , MRC Superficial Bladder Cancer Group Mitomycin-C Trial Collaborators (2003) Can p53 staining be used to identify patients with aggressive superficial bladder cancer? The Journal of Pathology, 200 (1), 74-81. (doi:10.1002/path.1293).

Record type: Article

Abstract

Approximately 10% of patients with superficial bladder cancer (pTa/pT1) recur with life-threatening muscle-invasive disease. Identification of these patients has been a major goal of bladder cancer research. In 1994, it was suggested that p53 immunostaining could identify the cancers that would progress and it was proposed that tumours that stain for p53 should be treated aggressively with radiotherapy or cystectomy. Despite the hundreds of studies published since on the relationship between p53 and progression in superficial bladder cancer, the clinical utility of p53 immunostaining has not been resolved because of limitations concerning the numbers of patients and the length of follow-up. This study set out to overcome these limitations by using tissue from a large multicentre trial that recruited 502 patients with a median follow-up of 10 years. Each of 34 patients that had progressed with >/= pT2 disease or had distant metastases or had died from bladder cancer was compared with one or two matched controls. Sections were stained with a mouse monoclonal antibody to p53, pAb1801. In agreement with many of the earlier studies, p53 immunostaining had prognostic significance. The adjusted hazard ratio for time to progression for the pAb1801-positive versus negative group was 2.5, with 95% confidence intervals of 1.05-5.98 (p = 0.039). The other major risk factor that is associated with progression of superficial bladder cancer is pT1G3 disease. Of the 42 pT1G3 cancers, 14 (33%) progressed. The proportion of cancers with p53 staining that progressed was similar to the proportion of pT1G3 cancers that progressed, but neither the sensitivity nor the specificity of association of p53 staining with progression is sufficient to recommend cystectomy in individual patients.

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More information

e-pub ahead of print date: 20 February 2003
Published date: May 2003
Keywords: Antibodies, Monoclonal, Disease Progression, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Proteins, Risk Factors, Time Factors, Tumor Suppressor Protein p53, Urinary Bladder Neoplasms, Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Organisations: Clinical Trials Unit

Identifiers

Local EPrints ID: 406330
URI: http://eprints.soton.ac.uk/id/eprint/406330
ISSN: 0022-3417
PURE UUID: fa42758a-1ba3-4af8-bcf3-026a85f4887a
ORCID for Gareth O. Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

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Date deposited: 10 Mar 2017 10:44
Last modified: 16 Mar 2024 04:19

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Contributors

Author: John R.W. Masters
Author: Urvi D. Vani
Author: Kenneth M. Grigor
Author: Angela Crook
Author: Mahesh K.B. Parmar
Author: Margaret A. Knowles
Corporate Author: MRC Superficial Bladder Cancer Group Mitomycin-C Trial Collaborators

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