title: Can p53 staining be used to identify patients with aggressive superficial bladder cancer?
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.
authors.affiliation: Institute of Urology, University College London, 3rd Floor, 67 Riding House Street, London W1W 7EJ, UK. j.masters@ucl.ac.uk
authors.forename: John R W
authors.initials: JR
authors.lastname: Masters
authors.forename: Urvi D
authors.initials: UD
authors.lastname: Vani
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Grigor
authors.forename: Gareth O
authors.initials: GO
authors.lastname: Griffiths
authors.forename: Angela
authors.initials: A
authors.lastname: Crook
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Knowles
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D012307:Risk Factors; D013997:Time Factors; D016159:Tumor Suppressor Protein p53; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*
chemical_list: D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53